Co occuring disorders-sum3


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Co occuring disorders-sum3

  1. 1. Co-occurring Addiction andLess SevereMental DisordersRichard Ries MDrries@u.washington.eduHarborview Medical CenterUniversity of WashingtonSeattle, Wa
  3. 3. Examples of Dual Disorders: MENTAL DISORDERS Schizophrenia Bi-polar Schizoaffective Major Depression BorderlinePersonality Post TraumaticStress Social Phobia others ADDICTIONDISORDERS AlcoholAbuse/Depen. Cocaine/ Amphet Opiates Marijuana Polysubstancecombinations Prescription drugs
  4. 4. Dual Disorders for Everyone? If applied to all cases, Term has no meaning (eg Spider phobia and “Running Addiction”) Both Mental and Addiction Disorders need to be overthreshold Personality Disorders, other than Borderline not usuallycounted Substance Induced Disorders cause diagnostic confusion
  5. 5. CHARACTERISTICS OF THE DUAL DIAGNOSISCLIENT IN KING COUNTY… Ries „89Severity ofChemical DependencyHighSeverity ofPsychiatric LowConditionLowHigh124 3LH HHLL HL
  6. 6. Systems Problems Different Laws…commitment/confid. Different funding..audits etc Different personnel Different training Different certification Different sites Different Norms
  7. 7. The Four Quadrant Framework forCo-Occurring DisordersA four-quadrantconceptual frameworkto guide systemsintegration and resourceallocation in treatingindividuals with co-occurring disorders(NASMHPD,NASADAD,1998; NY State; Ries,1993; SAMHSA Reportto Congress, 2002)Not intended to be usedto classify individuals(SAMHSA, 2002),but . . .Less severemental disorder/less severesubstanceabuse disorderMore severemental disorder/less severesubstanceabuse disorderMore severemental disorder/more severesubstanceabuse disorderLess severemental disorder/more severesubstanceabuse disorderHighseverityHighseverityLowseverity
  8. 8. DOUBLE TROUBLEHall ‟77 Poor out-pt attendance, discontinue RxAlterman ‟85 More mood changes, intensive staffingSolomon ‟86 More noncompliance, arrestsSafer ‟87 Over twice hosp. rate and criminal behavDrake ‟89 More hostility, noncomplianceBarbee ‟89 More psych symptomsLyons ‟89 More noncompliance, ER, jail, rehosp.Chen ‟92 Worse treatment course
  9. 9. But what about NON- severelymentally ill co-occurring pts? Like in Addiction Treatment settings Like in Criminal Justice settings Like in Primary Care Settings Like in ER‟s, especially with suicidal pts The new TIP will bring more focus onthese populations
  10. 10. Likelihood of a Suicide AttemptRisk Factor Cocaine use Major Depression Alcohol use Separation or DivorceNIMH/NIDAIncreased Odds OfAttempting Suicide62 times more likely41 times more likely8 times more likely11 times more likelyECA EVALUATION
  11. 11. Double Trouble:RELATIONSHIP OF ALCOHOL & DRUG PROBLEMSTO SEVERE SUICIDALITY (n=12,196)0.0%10.0%20.0%30.0%40.0%50.0%60.0%None(n=4853)Mild(n=1022)Moderate(n=2391)Severe(n=3930)ODDS: 1.23 ODDS: 1.18ODDS: 2.00ALCOHOL OR DRUG PROBLEMSPercentWithSevereSuicideRatingWalds = 235.41 p < .001 Ries & Russounpub , 2003ODDS adjustedfor age & gender
  12. 12. Drug Induced PsychopathologyDrug States Withdrawal Acute Protracted Intoxication Chronic UseSymptom Groups Depression Anxiety Psychosis Mania Rounsaville „90
  13. 13. Twelve-Month Prevalence of DSM-IV Independent Mood and AnxietyDisorders Among Respondents with DSM-IV Substance Use DisordersWho Sought Treatment in the Past 12 MonthsDisorder Respondents, % (SE)Those With Any Alcohol Use Disorder (5.81%)*Any mood disorder 40.69 (4.11)Major Depression 32.75 (4.01)Dysthymia 11.01 (2.74)Mania 12.56 (2.81)Hypomania 3.07 (1.37)Any anxiety disorder 33.38 (4.17)Panic disorderWith agoraphobia 4.10 (1.54)Without agoraphobia 9.10 (2.48)Social phobia 8.49 (3.48)Specific phobia 17.24 (3.10)Generalized anxiety disorder 12.35 (3.01)Any drug use disorder 33.05 (4.23)*Data in parentheses are the percentages of respondents with the substance use disorders whosought treatment in the past 12 months. Grant B, JAMA 2004
  14. 14. Twelve-Month Prevalence of DSM-IV Independent Mood and AnxietyDisorders Among Respondents with DSM-IV Substance Use DisordersWho Sought Treatment in the Past 12 MonthsDisorder Respondents, % (SE)Those With Any Drug Use Disorder (13.10%)*Any mood disorder 60.31 (5.86)Major Depression 44.26 (6.28)Dysthymia 25.91 (5.19)Mania 20.39 (5.17)Hypomania 2.48 (1.67)Any anxiety disorder 42.63 (5.97)Panic disorderWith agoraphobia 5.92 (2.19)Without agoraphobia 8.64 (3.05)Social phobia 12.09 (3.48)Specific phobia 22.52 (4.99)Generalized anxiety disorder 22.07 (5.18)Any alcohol use disorder 55.16 (6.29)*Data in parentheses are the percentages of respondents with the substance use disorders who soughttreatment in the past 12 months. Grant B, JAMA 2004
  15. 15. 49% of socialanxiety disorderpatients havepanic disorder**50% to 65% of panic disorderpatients have depression†11% of socialanxiety disorderpatients have OCD**67% of OCDpatients havedepression*70% of social anxietydisorder patients havedepressionComorbidity of Depressionand Anxiety DisordersDepressionOCDSocialAnxietyDisorderPanicDisorderHIGHLYCOMMON…HIGHLYCOMORBID
  16. 16. Diagnostic Criteria forPanic Attack• Palpitations, poundingheart• Sweating• Trembling or shakingAdapted with permission from American Psychiatric Association. Diagnostic and StatisticalManual of Mental Disorders, 4th ed. 1994.A discreet period of intense fear or discomfortin which 4 or more of the following symptomsdeveloped abruptly and reached a peak within10 minutes:
  17. 17. Diagnostic Criteria for PanicAttack Continued Dizziness Chills or hot flushes Feelings of unreality Fear of losingcontrol or goingcrazy Fear of dying Paresthesias Choking feeling Smothering orshortness of breath Chest pain ordiscomfort Abdominal distress
  18. 18. FatigueGastro-intestinalSymptomsSOMATICSYMPTOMSHeadacheChest PainDizzinessSomatic Symptoms InPanic Disorder
  19. 19. 1228271411162 21205101520253035Panic Disorder (N = 254)Major Depression (N = 738)Neither PDN or MD (N = 17,113)Quality of Life in Panic Disorder%Markowitz et al. Arch Gen Psychiatry. 1989;46:984.Marital Discord(past 2 weeks)Use Of ER(past year)FinancialDependence(welfare ordisability)
  20. 20. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4thed. 1994.DSM-IV Diagnostic Criteriafor PTSD Exposure to a traumatic event in whichthe person: experienced, witnessed, or wasconfronted by death or serious injury toself or othersAND responded with intense fear,helplessness,or horror
  21. 21. DSM-IV Diagnostic Criteriafor PTSD Continued Symptoms appear in 3 symptom clusters: re-experiencing, avoidance/numbing,hyperarousal last for > 1 month cause clinically significant distress orimpairment in functioning
  22. 22. DSM-IV Diagnostic Criteria forPTSD Re-experiencing Persistent re-experiencing of 1 of the following: recurrent distressing recollections of event recurrent distressing dreams of event acting or feeling event was recurring psychological distress at cues resembling event physiological reactivity to cues resemblingevent
  23. 23. DSM-IV Diagnostic Criteria forPTSD Avoidance/Numbing Avoidance of stimuli and numbing of generalresponsiveness indicated by 3 of the following: avoid thoughts, feelings, or conversations* avoid activities, places, or people* inability to recall part of trauma interest in activities estrangement from others restricted range of affect sense of foreshortened future
  24. 24. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4thed. 1994.DSM-IV Diagnostic Criteriafor PTSD Hyperarousal Persistent symptoms of increased arousal2: difficulty sleeping irritability or outbursts of anger difficulty concentrating hypervigilance exaggerated startle response
  25. 25. Prevalence of Trauma andProbability of PTSDProbability of PTSD010203040506070Witness Accident Threat w/WeaponPhysicalAttackMolestation Combat Rape%Prevalence of Trauma010203040%MaleFemaleWitness Accident Threat w/WeaponPhysicalAttackMolestation Combat Rape1212
  26. 26. 0255075100Vitality Social FunctionPTSDMDDOCDUS PopulationImpaired Quality of Life with PTSDSF-36 = 36 item short form health surveyLower score = more impairmentMalik M et al. J Trauma Stress. 1999;12:387-393.SF-36Score
  27. 27. Common Somatic ComplaintsOf Social Anxiety DisorderBeidel. J Clin Psychiatry. 1998;59(suppl 17):27.BlushingSweatingTremblingAnd Shaking“Butterflies”PalpitationsStuttering
  28. 28. Social Anxiety DisorderSPIN Screener Is being embarrassed or looking stupidamong your worst fears? Does fear of embarrassment cause you toavoid doing things or speaking to others? Do you avoid activities in which you arethe center of attention?Katzelnick et al. Presented at 37th Annual Meeting of the American College ofNeuropsychopharmacology; December 14-18, 1998; Los Croabas, Puerto Rico.
  29. 29. -20.0-15.0-10.0-5.00.0Impairment**(%)* LSAS score in controls = 25; ** Impairment (%) refers to percentage change in wages and percentagepoint changes in probabilities of college graduation and having a technical, professional, ormanagerial job.Wages CollegeGraduationProfessionalOrManagement PositionsKatzelnick et al. Presented at 37th Annual Meeting of the American College of Neuropsychopharmacology;December 14-18, 1998; Los Croabas, Puerto Rico.Social Anxiety Disorder: Educational andOccupational Impairment
  30. 30. Therapy PlanPsychBio LabsMeds (anti-depressants,etc.)Psych psychotherapyeducation groupsprocess groupsSocial Couples conf.D/C planninghousing, etc.CDLabsMeds (withdrawal, craving, etc.)Step workGroupsAA MeetingsInterventionSober housing
  31. 31. 1: JAMA. 2004 Apr 21;291(15):1887-96. Related Articles, LinksTreatment of depression in patients with alcohol or other drugdependence: a meta-analysis.Nunes EV, Levin FR.DATA SYNTHESIS: For the HDS score, the pooled effect size from the random-effects model was0.38 (95% confidence interval, 0.18-0.58). Heterogeneity of effect on HDS across studies wassignificant (P <.02), and studies with low placebo response showed larger effects.Moderator analysis suggested that diagnostic methods and concurrent psychosocial interventionsinfluenced outcome.Studies with larger depression effect sizes (>0.5) demonstrated favorable effects of medication onmeasures of quantity of substance use, but rates of sustained abstinence were low.CONCLUSIONS: Antidepressant medication exerts a modest beneficial effect forpatients with combined depressive- and substance-use disorders. It is not astand-alone treatment, and concurrent therapy directly targeting the addiction isalso indicated.More research is needed to understand variations in the strength of the effect, but the data suggestthat care be exercised in the diagnosis of depression-either by observing depression to persistduring at least a brief period of abstinence or through efforts by clinical history to screen outsubstance-related depressive symptoms.
  32. 32. : Psychopharmacol Bull. 1998;34(1):117-21.Related Articles, LinksFluoxetine versus placebo in depressed alcoholic cocaine abusers.Cornelius JR, Salloum IM, Thase ME, Haskett RF, Daley DC, Jones-Barlock A, Upsher C, Perel JM.All 51 patients participated in a double-blind, parallel group study of fluoxetine versus placebo in depressedalcoholics. The principal focus of this article is the one-third of the depressed alcoholics who also abused cocaineand how the treatment response of those 17 patients compared with that of the 34 depressed alcoholics who didnot abuse cocaine.During the study, no significant difference in treatment outcome was noted between the fluoxetine group(N = 8) and the placebo group (N = 9) for cocaine use, alcohol use, or depressive symptoms. In addition, nosignificant within-group improvement was noted for any of these outcome variables in either of the two treatmentgroups.Indeed, across the combined sample of 17 depressed alcoholic cocaine abusers, the mean Beck DepressionInventory (BDI) score worsened slightly from 19 to 21 during the course of the study, and 71 percent of thepatients continued to complain of suicidal ideations at the end of the study.The 17 cocaine-abusing depressed alcoholics showed a significantly worse outcome than the 34 non-cocaineabusing depressed alcoholics on the 24-item Hamilton Rating Scale for Depression (HAM-D) and BDI depressionscales and on multiple measures of alcohol consumption. These findings suggest that comorbid cocaineabuse acts as a robust predictor of poor outcome for the drinking and the depressive symptoms ofdepressed alcoholics.
  33. 33. Depress Anxiety. 2001;14(4):255-62. Related Articles, LinksParoxetine for social anxiety and alcohol use in dual-diagnosed patients.Randall CL, Johnson MR, Thevos AK, Sonne SC, Thomas SE, Willard SL, Brady KT, Davidson JR.Fifteen individuals meeting DSM-IV criteria for both social anxiety disorder and alcohol usedisorder were randomized to treatment. Paroxetine (n = 6) or placebo (n = 9) was given in adouble-blind format for 8 weeks using a flexible dosing schedule. Dosing began at 20 mg/dand increased to a target dose of 60 mg/d.There was a significant effect of treatment group on social anxiety symptoms, where patientstreated with paroxetine improved more than those treated with placebo on both theClinical Global Index (CGI) and the Liebowitz Social Anxiety Scale (Ps < or = 0.05).On alcohol use, there was not a significant effect of treatment on quantity/frequency measuresof drinking, but there was for the CGI ratings (50% paroxetine patients versus 11% placebopatients were improvers on drinking, P < or = 0.05).This pilot study suggests that paroxetine is an effective treatment for social anxiety disorder inindividuals with comorbid alcohol problems, and positive treatment effects can be seen in aslittle as 8 weeks. Further study is warranted to investigate its utility in helping affectedindividuals reduce alcohol use. Copyright 2001 Wiley-Liss, Inc.
  34. 34. Why aren‟t Antidepressants more effectivein addictions patients? Psychiatric outcomes: Antidepressants only beat placebo by 20% anyway in NONaddicts Study patients also get “addiction rx” Maybe addiction rx is more anti-dep, anti anx than we think…vizSchuckit 80% -> 20% This is poorly studied…maybe better with 12 step Sub Induced criteria are wrong Addictions outcomes Meds take focus off sobriety Meds reinforce sobriety Just don‟t work for this
  35. 35. Alcohol Clin Exp Res. 2001 Feb;25(2):210-20.Concurrent alcoholism and social anxiety disorder: a first step towarddeveloping effective treatments.Randall CL, Thomas S, Thevos AK.The present study investigated whether simultaneous treatment of social phobia and alcoholism, comparedwith treatment of alcoholism alone, improved alcohol use and social anxiety for clients with dual diagnosesof social anxiety disorder and alcohol dependence.METHODS: The design was a two-group, randomized clinical trial that used 12 weeks of individual cognitivebehavioral therapy for alcoholism only (n = 44) or concurrent treatment for both alcohol and social anxietyproblems (n = 49). Outcome data were collected at the end of 12 weeks of treatment and at 3 months afterthe end of treatment.RESULTS: Results with intent-to-treat analyses showed that both groups improved on alcohol-relatedoutcomes and social anxiety after treatment.Counter to the hypothesis, the group treated for both alcohol and social anxietyproblems had worse outcomes on three of the four alcohol use indices.No treatment group effects were observed on social anxiety indices.CONCLUSIONS: Implications for the staging of treatments for coexisting social phobia and alcoholism arediscussed, as well as ways that modality of treatments might impact outcomes.
  36. 36. J Subst Abuse Treat. 2003Sep;25(2):99-105.Related Articles, LinksA cognitive-behavioral treatment for incarcerated women withsubstance abuse disorder and posttraumatic stress disorder: findingsfrom a pilot study.Zlotnick C, Najavits LM, Rohsenow DJ, Johnson DM.This preliminary study evaluates the initial efficacy of a cognitive-behavioral treatment,Seeking Safety, as an adjunct to treatment-as-usual in an uncontrolled pilot study ofincarcerated women with current SUD and comorbid PTSD.Of the 17 incarcerated women with PTSD and SUD who received Seeking Safety treatmentand had outcome data,results show that nine (53%) no longer met criteria for PTSD at the end oftreatment; at a followup 3 months later, seven (46%) still no longer met criteriafor PTSDAdditionally, there was a significant decrease in PTSD symptoms from intake to posttreatment,which was maintained at the 3-month followup assessment.Based on results from a diagnostic interview and results of urinalyses, six (35%) of thewomen reported the use of illegal substances within 3 months from release fromprison. Measures of client satisfaction with treatment were high. Recidivism rate (return toprison) was 33% at a 3-month followup.
  37. 37. Can encouraging substance abuse patients to participate inself-help groups reduce demand for health care?A quasi-experimental studyn=1774, 1 year follow-up Humphreys et al ..2001Outpt Inpt days AbstinenceVisits Rates 12 Step 13.1 10.5 45.7 Cog Beh 17 17 36.2* all p< .001 ** 64% higher cost for CBT
  38. 38. Dual Screening: the “Dual Cage”…………….easy, but no data ASAM pt placement………..needs experience, little or no data ASI psych…………………….short, available, good screening, good data Beck, Zung, Ham D etc…..easy, good data, may be limited Brief Symptom Inventory…easy, broad symptom mix Others……………………………see new Co-occurring TIP in 12-04
  39. 39. “Dual CAGE” QUESTIONS Cut Down (or stopped) Because mental symptoms worsened Because MH doctor or therapist suggested Annoyed when drug/alc. use discussed Annoyed, anxious or angry,… fights when using Admitted to ER or hospital for psych when using ornot ADHD when child Guilty about use Guilty, depressed, suicidal when using or not Ever made a suicide attempt when using or not
  40. 40. CAGE Questions Eye opener: taken drink or drug in AM to feelbetter Taken a drink or drug to blot out symptoms Taken drink or drug with psych med Not taken meds because of using drug/alc(forgot, avoid mixing, etc.) What are 2 or 3 reasons you use alc/drugs? What are 2 or 3 reasons you might want to stopor cut down?
  41. 41. Medications Essential to Treatment of Severely Mentally Ill Substance Use and Not-Taking Meds are the 2 topreasons for De-Comp Should be part of court orders Monitored by Case managers, nurses, doctors For Dep/Anx, less clear Personal experience shows maximizing 12 step ANDuse of meds is best rx
  42. 42. It may not be that the med(s) stoppedworking, but…… The patient stopped the med The patient stopped the med AND used drugsand/or alcohol…... OR lowered the med and used… OR used on top of the med…. OR used twice the dose on one day andnothing the next…. Stimulants ( cocaine/amphets) are most MSEdestructive.
  43. 43. How to use AA as a treatmentpartner 1. Know something about AA, its history,presence in your community, structure andcontent 2. Helpful Readings: Brown: A psychological view of the 12 steps AA: AA for the medical practitioner; and The AA member and medications Twelve Step Facilitation Therapy Manual- Project Match, NIAAA web site Forman: “One AA Meting doesn‟t fit all”
  44. 44. One year ABSTINENCE was predicted by:• AA involvement (OR=2.9), ( n=377)• not having pro-drinking influences in ones network(OR=0.7• having support for reducing consumption from people metin AA (versus no support; OR=3.4).• In contrast, having support from non-AA members wasnot a significant predictor of abstinence.Kaskutas: Addiction 2002
  45. 45. Double Trouble Recovery (DTR)Outcomes Members of 24 DTR groups (n=240) New York City, 1year outcomes Drug/alcohol abstinence = 54% at baseline, increased to72% at follow-up. More attendance = better Medication adherence, Better Medication adherence = less hospitalization Magura Add Beh 2003, Psych Serv 2002
  46. 46. Dual Dep/Anx RX plan Differential Dx 12 step facilitation Meds if indicated ( and I often use them) Visits: Ries 1/week ( 12 step facil and meds) AA 3x week or 90 in 90 Meet with sponsor Meet with family
  47. 47. Low mental illness/High addictions outpt gets In most MHC‟s: MD visit q 3 months CM visit q 2 wks…focus on ADL‟s Maybe dual dx group 1-2 hrs/wk Limited expectations of recovery Pschotherapy time ~ 0-2 hrs week In the most Addictions IOP‟s MD visit 1/ 3 months, often 1‟ care CM 1:1 q 2 wks….focus on Sub use, U tox‟s IOP group 3 hrs-3x week Expectations of Sobriety/progress Psychotherapy time 3-10 hrs week ( plus more AA)
  48. 48. Report Questions Ability of National Treatment Infrastructure to Deliver Quality Care301-405-9770 (voice) 301-403-8342 (fax)   CESAR FAX is supported by VOIT 1996-1002, awarded by the U.S. Department of Justice through the Governor‟s Office of Crime Control and Prevention.CESAR FAX may be copied without permission. Please cite CESAR as the source.Percentageof ProgramsClosed or StoppedServicesReorganized Director inPosition Less ThanOne YearNo InformationServices, E-mail,or Voicemail0%20%40%60%80%100%15%25%54%20%SOURCE: Adapted by CESAR from the McLellan, A. T., Carise, D., and Kleber, J., “Can the National Addiction Treatment Infrastructure Support the Public‟sDemand for Quality Care?” Journal of Substance Abuse Treatment 25(2):117-121, 2003. For more information, contact Dr. A. Thomas McLellan
  49. 49. New Issues in Medications forCo-occurring Addiction andMental DisordersRichard Ries MD
  50. 50. Medication monitoring andmotivating Know who is on what and what for Know the prescriber if possible Sit in on med sessions onsite Talk to off-site doctor or nurse PRE problem!!! Know something about meds… ATTC Tech transfer centers summary New COD TIP ( Dec 04) NIMH web site, NAMI web site
  51. 51. Medications: counselor‟s role Ask the pt about : Compliance… “sometimes people forget their medications…how often doesthis happen to you?” …ie % not taking Effectiveness… “how well do you think the meds are working?… what do you notice… here is what I notice Side Effects…. “ are you having any side effects to the medication?… what are they… have you told the prescriber? do you need help with talking to the presciber?
  52. 52. Medications….potential problems Can reinforce addiction denial if recovery is notintegrated and supported…esp by theprescriber..( so work with them) Can be expensive, cause side effects, could beused in overdose. Encumber the pt with seeing MD, or mentalhealth system, cost, convenience etc….ie makesure they are really necessary. Active participation in recovery can be bothantidep and antianx…but if these problemscontinue, or disrupt recovery, meds should beconsidered
  53. 53. Antipsychotics
  54. 54. Alcohol Clin Exp Res. 2004 May;28(5):736-45.A double-blind, placebo-controlled study of olanzapine in thetreatment of alcohol-dependence disorder.Guardia J, Segura L, Gonzalvo B, Iglesias L, Roncero C, Cardus M, Casas M.METHODS: A total of 60 alcohol-dependent patients were assigned to 12 weeks treatmentwith either olanzapine or placebo. The primary variable relapse to heavy drinking rate wasevaluated by means of intention-to-treat analyses. Alcohol consumption, craving, adverseevents, and changes in the biochemical markers of heavy drinking and possible toxicity werealso evaluated.RESULTS: We did not find significant differences in the survival analysis between placebo andolanzapine-treated patients (Kaplan-Meier log rank = 0.46, df = 1, p = 0.50). Eleven (37.9%)patients treated with olanzapine relapsed compared with 9 (29%) of those receiving placebo(chi = 0.53, df = 1, p = 0.5). Although some adverse events (weight gain, increased appetite,drowsiness, constipation, and dry mouth) were found more frequently in the olanzapine group,differences did not reach statistical significance in comparison with the placebo group.CONCLUSIONS: We found no differences in relapse rate or other drinking variableswhen comparing olanzapine with placebo-treated patients.
  55. 55. J Clin Psychopharmacol. 2000Feb;20(1):94-8.Effects of clozapine on substance use in patients with schizophreniaand schizoaffective disorder: a retrospective survey.Zimmet SV, Strous RD, Burgess ES, Kohnstamm S, Green AI.. The authors report data from a retrospective survey of substance use in 58patients treated with clozapine who had a history of comorbid schizophrenia (orschizoaffective disorder) and substance use disorder. Of these 58 patients, 43 werebeing treated with clozapine at the time of the survey; the remaining 15 patients haddiscontinued clozapine before the survey.More than 85% of the patients who were active substance users at the time ofinitiation of treatment with clozapine decreased their substance use over thecourse of clozapine administration. For patients who continued treatment withclozapine up to the present, the decrease in substance use was strongly correlatedwith a decrease in global clinical symptoms.
  56. 56. First episode schizophrenia-related psychosis and substance use disorders:acute response to olanzapine and haloperidol.Green AI, Tohen MF, Hamer RM, Strakowski SM, Lieberman JA, Glick I, Clark WS; HGDH Research Group.METHODS: The study involved 262 patients. Patients with a history of substancedependence within 1 month prior to entry were excluded.RESULTS: Of this sample, 97 (37%) had a lifetime diagnosis of substance use disorder(SUD); of these 74 (28% of the total) had a lifetime cannabis use disorder (CUD) and 54 (21%) hada lifetime diagnosis of alcohol use disorder (AUD).•Those with CUD had a lower age of onset than those without.•Patients with SUD were more likely to be men.•Patients with SUD had more positive symptoms and fewer negative symptoms thanthose without SUD, and they had a longer duration of untreated psychosis.•The 12-week response data indicated that 27% of patients with SUD were responderscompared to 35% of those without SUD.•Patients with AUD were less likely to respond to olanzapine than those without AUD.DISCUSSION: These data suggest that first-episode patients are quite likely to have comorbidsubstance use disorders, and that the presence of these disorders may negatively influenceresponse to antipsychotic medications, both typical and atypical antipsychotics, over the first 12weeks of treatment.Schizophr Res. 2004 Feb 1;66(2-3):125-35.
  57. 57. Bipolar Disord. 2002Dec;4(6):406-11.Related Articles, LinksQuetiapine in bipolar disorder and cocaine dependence.Brown ES, Nejtek VA, Perantie DC, Bobadilla L.METHODS: Open-label, add-on, quetiapine therapy was examined for 12 weeks in 17outpatients with bipolar disorder and cocaine dependence. Subjects were evaluated with astructured clinical interview; Hamilton Depression Rating (HDRS), Young Mania Rating(YMRS), Brief Psychiatric Rating (BPRS) scales; and Cocaine Craving Questionnaire (CCQ).Urine samples and self-reported drug use were also obtained. Data were analyzed using a lastobservation carried forward method on all subjects given medication at baseline.RESULTS:Significant improvement from baseline to exit was observed in HDRS, YMRS, BPRS andCCQ scores (p < or = 0.05).Dollars spent on cocaine and days/week of cocaine use decreased non-significantly,and urine drug screens did not change significantly from baseline to exit.Quetiapine was well tolerated, with no subjects to our knowledge discontinuing because ofside-effects. CONCLUSIONS: The use of quetiapine was associated with substantialimprovement in psychiatric symptoms and cocaine cravings. The findings are promising andsuggest larger controlled trials of quetiapine are needed in this population.
  58. 58. Schizophr Res. 2003 Mar 1;60(1):81-5.Alcohol and cannabis use in schizophrenia: effects of clozapine vs.risperidone.Green AI, Burgess ES, Dawson R, Zimmet SV, Strous RD.METHOD: This study involved retrospective assessment of abstinence(cessation of alcohol and cannabis use) in 41 patients treated with eitherrisperidone (n=8) or clozapine (n=33) for at least 1 year. In 32 of these 41patients, information was available on whether abstinence occurred duringthe 1-year period.RESULTS: Abstinence rates were significantly higher in patientstreated with clozapine than in those treated with risperidone (54% vs.13%, p=0.05).
  59. 59. Eur J Pharmacol.2003 May9;468(2):121-7.Risperidone reduces limited access alcohol drinking in alcohol-preferring rats.Ingman K, Honkanen A, Hyytia P, Huttunen MO, Korpi ER.Department of Pharmacology and Clinical Pharmacology, University of Turku,Itainen Pitkakatu 4, FIN-20520, Turku, FinlandAn atypical antipsychotic drug risperidone reduced ethanol drinking ofethanol-preferring Alko, Alcohol (AA) rats in a limited access paradigm. Itseffect was transient at a dose known to preferentially antagonize the 5-HT(2)receptors (0.1 mg/kg, s.c.), but long-lasting when the dose was increased to 1.0mg/kg that also blocks dopamine D(2) receptors.
  60. 60. Can J Psychiatry. 2002Sep;47(7):671-5.Related Articles, LinksRisperidone decreases craving and relapses in individuals withschizophrenia and cocaine dependence.Smelson DA, Losonczy MF, Davis CW, Kaune M, Williams J, Ziedonis D.OBJECTIVE: To examine the efficacy of atypical neuroleptics for decreasing craving and drug relapsesduring protracted withdrawal in individuals dually diagnosed with schizophrenia and cocaine dependence.METHOD: We conducted a 6-week, open-label pilot study comparing risperidone with typical neuroleptics ina sample of withdrawn cocaine-dependent schizophrenia patients.RESULTS: Preliminary results suggest that individuals treated with risperidone had significantly lesscue-elicited craving and substance abuse relapses at study completion. Further, they showed atrend toward a greater reduction in negative and global symptoms of schizophrenia.CONCLUSION: Atypical neuroleptics may help reduce craving and relapses in this population. Futureresearch should include more rigorous double-blind placebo-controlled studies with this class ofmedications.
  61. 61. Comorbid Substance Abuse Associated WithNoncompliance in Schizophrenia Nearly half of all patients ina prospective 4-year study(N = 99) were activesubstance abusers (n = 42) Patients who activelyabused substances weresignificantly more likely tobe noncompliant67%47%34%020406080No PastHistoryPastHistoryCurrentUserP < 0.05%NoncompliantHunt GE et al. Schizophrenia Res. 2002;54:253-264.
  62. 62. It may not be that the med(s)stopped working, but…… The patient stopped the med The patient stopped the med AND useddrugs and/or alcohol…... OR lowered the med and used… OR used on top of the med…. OR used twice the dose on one day andnothing the next…. Stimulants ( cocaine/amphets) are mostMSE destructive.
  63. 63. RISPERDAL® CONSTA™Injection Kit ComponentsNeedle Pro® DeviceSafety NeedleSmartSite®AccessDeviceRisperidoneMicrospheresAqueousDiluentAssembledRISPERDAL® CONSTA™PRC approved withchanges: 11/10/03(RISPERDAL CONSTAPromotional slide kit)
  64. 64. *25-mg dose, N = 14.Data on file, Janssen Pharmaceutica Products, L.P.Risperidone+9-hydroxyrisperidone(ng/mL)Time (wk)0 1 2 3 4 5 6 7 8 9 10 11 12Blood Levels Over Time AfterSingle Dose*PRC approved withchanges: 11/10/03(RISPERDAL CONSTAPromotional slide kit)AntipsychoticSupplementation
  65. 65. Substance Induced Psychoses Amphet/Methamphetamines Cocaine Ecstacy Hallucinogens ( strong THC too) Other Rave Drugs Alcohol WD and Hallucinosis
  66. 66. Anticonvulsants
  67. 67. COMPARING THE KNOWN EFFICACY OFANTIEPILEPTIC AGENTS IN BIPOLAR DISORDERDrug Mania Depression Maintenance CommentsValproate New Depakote ERFormulationCarbamzepine 2 new maintenance studiesv. lithiumGabapentin — 2 negative placebo-controlled studies in maniaLamotrigine  Antidepressant activity inseveral controlled trialsTopiramate Dose-related weight lossKey: Efficacy demonstrated in > 2 placebo-controlled trialsEfficacy demonstrated in one placebo-controlled or two large, activecomparator trialsEfficacy in two small or one large active comparator trialEfficacy only in open trials and case series Conflicting evidence of efficacy in available studies— Lack of efficacy demonstrated in randomized, controlled trialsND No data presently availableKeck & McElroy, 2002
  68. 68. COMPARING THE KNOWN EFFICACY OFANTIEPILEPTIC AGENTS IN BIPOLAR DISORDERDrug Mania Depression Maintenance CommentsOxcarbazepine Improved tolerability &pharmacokineticsZonisamide ND ND May produce weight lossin some patientsTiagabine  ND ND More data neededregarding tolerability andefficacyLevetiracetam ND ND ND Data needed regardingefficacy and tolerabilityKey: Efficacy in two small or one large active comparator trialEfficacy only in open trials and case series Conflicting evidence of efficacy in available studiesND No data presently availableKeck & McElroy, 2002
  69. 69. Eur Neuropsychopharmacol. 2004Aug;14(4):319-23.Related Articles, LinksHow real are patients in placebo-controlled studies of acute manic episode?Storosum JG, Fouwels A, Gispen-de Wied CC, Wohlfarth T, van Zwieten BJ, van den Brink W.OBJECTIVE: To determine whether the results from placebo-controlled studies conducted inpatients with manic episode can be generalised to a routine population of hospitalised acutemanic patients.METHODS: A list of four most prevalent inclusion and the nine most prevalent exclusioncriteria was constructed for participation in previous randomised-controlled trials (RCTs). Onthe basis of this list, a consecutive series of 68 patients with 74 episodes of acute mania whohad been referred for routine treatment were retrospectively assessed to determine theireligibility for a hypothetical but representative randomised controlled trial.RESULTS: Only 16% of the manic episodes would qualify for the hypothetical trial (maleepisodes 28%, female episodes 10%),….whereas 37%, 20% and 27% of the manic episodes would have to be excluded becausethey did no fulfil one, two or at least three of the inclusion or exclusion criteria. CONCLUSION:Only a small percentage acute manic episodes in a routine mental hospital seem toqualify for a standard placebo-controlled RCT.. These notions should be taken into accountwhen evaluating the results of RCTs in bipolar patients with an acute manic episode.
  70. 70. Am J Addict 2002Spring;11(2):141-50The differential effects of medication on mood, sleep disturbance, andwork ability in outpatient alcohol detoxification.Malcolm R, Myrick H, Roberts J, Wang W, Anton RF.A double-blind, randomized controlled trial of patients (n = 136) meeting DSM-IVcriteria for alcohol withdrawal and stratified based on detoxification history weretreated with carbamazepine or lorazepam for 5 days on a fixed dose taperingschedule. Mood symptoms improved for all subjects regardless of medication ordetoxification history.•main effect favoring carbamazepine in reducing anxiety (p = 0.0007).•main effect of medication on sleep that again favored carbamazepine (p =0.0186).In this study of outpatients with mild to moderate alcohol withdrawal,carbamazepine was superior to lorazepam in reducing anxiety and improving sleep.
  71. 71. Alcohol Clin Exp Res 2001Sep;25(9):1324-9Related Articles, Books, LinkOutDivalproex sodium in alcohol withdrawal: a randomizeddouble-blind placebo-controlled clinical trial.Reoux JP, Saxon AJ, Malte CA, Baer JS, Sloan KL.Veterans Affairs Puget Sound Health Care System andDepartment of Psychiatry, University of Washington School ofMedicine, Seattle, Washington 98108,
  72. 72. Psychiatr Serv. 2000 May;51(5):634-8. Related Articles, LinksChanges in use of valproate and other mood stabilizers for patientswith schizophrenia from 1994 to 1998.Citrome L, Levine J, Allingham B.METHODS: For each calendar year from 1994 through 1998, data were drawn froma database containing clinical and drug prescription information for every inpatientin the adult civil facilities of the New York State Office of Mental Health.RESULTS: In 1994 a total of 26.2 percent of inpatients diagnosed as havingschizophrenia received a mood stabilizer, compared with 43.4 percent in 1998. In1994 lithium was the most commonly prescribed mood stabilizer, for 13.2 percent ofpatients, followed by valproate, for 12.3 percent. In 1998 valproate was the mostcommonly prescribed, for 35 percent of patients, followed by lithium, for 11.3percent. On average, patients received valproate for about two-thirds of theirhospital stay, at a mean dose of 1,520 mg per day.CONCLUSIONS: The adjunctive use of valproate nearly tripled from 1994 to1998 among patients with a diagnosis of schizophrenia. Valproate has becomethe most commonly prescribed mood stabilizer for this population, despite thepaucity of evidence in the literature for efficacy in this use. Controlled clinical trialsare needed to examine the adjunctive use of mood stabilizers, in particularvalproate, among patients with schizophrenia.
  73. 73. Psychiatr Serv. 2004 Mar;55(3):290-4. Related Articles, LinksAdjunctive divalproex and hostility among patients with schizophreniareceiving olanzapine or risperidone.Citrome L, Casey DE, Daniel DG, Wozniak P, Kochan LD, Tracy KA.METHODS: A total of 249 inpatients with schizophrenia were randomly assigned,RESULTS: Combination treatment with risperidone or olanzapine plus divalproexwas associated with different scores on the hostility item of the PANSS comparedwith antipsychotic monotherapy.•This result was not seen beyond the first week of treatment, but there was atrend toward a difference in effect for the entire treatment period.•Combination therapy had a significantly greater antihostility effect at days 3and 7 than monotherapy.•The effect on hostility appears to be statistically independent ofantipsychotic effect on other PANSS items reflecting delusional thinking,a formal thought disorder, or hallucinations.CONCLUSIONS: Divalproex sodium may be useful as an adjunctive agent inspecifically reducing hostility in the first week of treatment with risperidone orolanzapine among patients with schizophrenia experiencing an acute psychoticepisode.
  74. 74. J Clin Psychopharmacol. 2001Feb;21(1):21-6.Related Articles, LinksDivalproex sodium augmentation of haloperidol in hospitalizedpatients with schizophrenia: clinical and economic implications.Wassef AA, Hafiz NG, Hampton D, Molloy M.Divalproex sodium has been approved for use in treating bipolar disorder. Itsusefulness in schizophrenia has yet to be adequately assessed.Compared with those who received no or delayed augmentation, the early-augmentation group required 44.8% fewer inpatient days from the initiation ofhaloperidol treatment. Patient response to treatment was particularly noted insuspiciousness, hallucinations, unusual thought content, and emotional withdrawal.Early augmentation with valproate may reduce the length of inpatient staysand provide substantially better therapeutic outcomes. It is, however,premature to recommend changes in the standard clinical management ofschizophrenia on the basis of the data provided herein, in view of the small sampleand open-label nature of the report.
  75. 75. Depakote with Atypical Antipsychotic: lipidsPatients treated with a combination of Depakote and Zyprexa experienced aminimal increase in total cholesterol compared to the greater increase inpatients treated with Zyprexa when used as monotherapy:+26.62 mg/dL for Zyprexa monotherapy (baseline: 193 mg/dL).+0.87 mg/dL for Depakote plus Zyprexa (baseline: 198 mg/dL).Patients treated with a combination of Depakote and Risperdal experienced adecrease in total cholesterol compared to Risperdal when used asmonotherapy:+9.64 mg/dL for Risperdal monotherapy (baseline: 188 mg/dL).-13.44 mg/dL for Depakote plus Risperdal (baseline: 192 mg/dL).Patients in the Zyprexa monotherapy group had the highest rate of shift from anormal total cholesterol (<200 mg/dL) to a high total cholesterol (>200 mg/dL).Casey et al APA conv 2004
  76. 76. Lancet. 2003 May 17;361(9370):1677-85.Oral topiramate for treatment of alcohol dependence: arandomised controlled trial. Johnson BA et alMETHODS: double-blind randomised controlled 12-week clinical trialcomparing oral topiramate and placebo for treatment of 150 individuals withalcohol dependence..FINDINGS: At study end, participants on topiramate, compared withthose on placebo, had• 2.88 (95% CI -4.50 to -1.27) fewer drinks per day (p=0.0006),• 3.10 (-4.88 to -1.31) fewer drinks per drinking day (p=0.0009),• 27.6% fewer heavy drinking days (p=0.0003),• 26.2% more days abstinent (p=0.0003), and a• log plasma gamma-glutamyl transferase ratio of 0.07 (-0.11 to -0.02) less (p=0.0046).Topiramate-induced differences in craving were also significantly greater thanthose of placebo, of similar magnitude to the self-reported drinking changes,and highly correlated with them.
  77. 77. Topiramate for Alcohol Withdrawal:1: Med Arh. 2002;56(4):211-2.A pilot study of Topiramate (Topamax) in the treatment of tonic-clonic seizuresof alcohol withdrawal syndromes. Rustembegovic A, Sofic E, Kroyer G. AntonProksch Institute, Vienna, Austria.12 patients with median age of 49.5 years and median body weight of76.3 kg were treated with topiramate twice daily for up 30 days, starting with adose of 50 mg in the morning and 50 mg in the evening.The preliminary findings of this study suggest that topiramate isvery effective against tonic-clonic seizures in alcohol withdrawalsyndrome. No side effects were observed. Only two patients had loss of bodyweight (3-3.5 kg/4 weeks).
  78. 78. J Clin Psychopharmacol. 2004 Aug;24(4):374-8. Vieta E,et alEffects on weight and outcome of long-term olanzapine-topiramate combination treatment in bipolar disorder.Twenty-six Diagnostic and Statistical Manual of Mental Disorders, FourthEdition bipolar spectrum patients received olanzapine plus topiramate cotherapy fortreatment of their manic (n = 14), hypomanic (n = 6), depressive (n = 2), and mixed (n =1) symptoms for 1 year. Three rapid cycling patients were also enrolled despite beingeuthymic. Thirteen (50%) patients completed the 1-year follow-up.By intent-to-treat, patients significantly improved from baseline in• Young Mania Rating Scale scores (P < 0.0001),• Hamilton Depression Rating Scale (P < 0.05), and• Modified Clinical Global Impressions for Bip (mania P < 0.0001,• Depression ( Ham) P < 0.05, ………overall P < 0.0001).Most patients gained weight during the first month of combined treatment (meanweight gain 0.7 +/- 0.6 kg), but at the 12-month endpoint, the mean weight changewas -0.5 +/- 1.1 kg.
  79. 79. Subst Abus. 2003 Jun;24(2):29-32.Gabapentin for the treatment of ethanol withdrawal.Voris J, Smith NL, Rao SM, Thorne DL, Flowers QJ.We retrospectively report on the use of gabapentin for ethanol withdrawal in 49patients. Thirty-one patients were treated in the outpatient program and 18 in thegeneral inpatient psychiatric unit.Positive outcomes as evidenced by completion of gabapentin therapy wereachieved in 25 out of 31 outpatients and 17 out of 18 inpatients.Statistical significance was reached regarding the positive relationship betweenprior ethanol use and inpatient "as needed" benzodiazepine use. Both sets of datasuggest that gabapentin works well for the mild to moderate alcohol withdrawalpatient.
  80. 80. Psychiatry Clin Neurosci. 2003Oct;57(5):542-4.Related Articles, LinksOpen pilot study of gabapentin versus trazodone to treat insomnia inalcoholic outpatients.Karam-Hage M, Brower KJ.Alcohol-dependent outpatients with persisting insomnia were treated with either gabapentin ortrazodone. Patients were assessed at baseline and after 4-6 weeks on medication using theSleep Problems Questionnaire (SPQ). Of 55 cases initially treated, 9% dropped out due tomorning drowsiness. Of the remaining 50 cases, 34 were treated with gabapentin (mean dose+/- SD = 888 +/- 418 mg) at bedtime and 16 were treated with trazodone (105 +/- 57 mg) atbedtime.Both groups improved significantly on the SPQ but the gabapentin group improvedsignificantly more than the trazodone group. Controlled studies are warranted toreplicate these findings.
  81. 81. Med Arh. 2004;58(1):5-6.A study of gabapentin in the treatment of tonic-clonicseizures of alcohol withdrawal syndrome.Rustembegovic A, Sofic E, Tahirovic I, Kundurovic Z.In this study for thirty (30) patients with alcohol withdrawal syndrome, theresponse to anticolvusant gabapentin was assessed. Thirty (30) patientswith median age of 57.0 years and median body weight of 79.1 kg weretreated with gabapentin 3 x 300 mg daily for up 30 days.The preliminary findings of this study suggest that gabapentin is veryeffective against tonic-clonic seizures in alcohol withdrawalsyndrome.Gabapentin was safe and well tolerated. For twenty (20) patients no sideeffect were observed.
  82. 82. J Clin Psychiatry. 2003 Feb;64(2):197-201. Related Articles, LinksLamotrigine in patients with bipolar disorder and cocaine dependence.Brown ES, Nejtek VA, Perantie DC, Orsulak PJ, Bobadilla L.METHOD: Lamotrigine was started at a dose of 25 mg/day (12.5 mg/day in those takingvalproic acid) and titrated to a maximum dose of 300 mg/day. The subjects consisted of 13men and 17 women with cocaine dependence and bipolar I disorder (N = 22), bipolar IIdisorder (N = 7), or bipolar disorder not otherwise specified (N = 1), with a mean +/- SD age of35.4 +/- 7.2 years. Data were analyzed using the last observation carried forward on allsubjects who completed the baseline evaluation and at least 1 postbaseline assessment.RESULTS: Significant improvement was observed in HAM-D, YMRS, and BPRS scores(p < or =.02). Cravings also significantly decreased as measured by the CCQ (p <.001).Dollar amount spent on drugs decreased nonsignificantly. Lamotrigine was welltolerated, with no subjects discontinuing due to side effects.CONCLUSION: Lamotrigine treatment was well tolerated in this sample and associated withstatistically significant improvement in mood and drug cravings but not drug use. The findingssuggest that larger controlled trials of lamotrigine are needed in this population.
  83. 83. Anti-opiate Addiction Meds Harm reduction:..opiates Methadone Only through Methadone agencies for Addiction Confusion when injury/pain/addiction co-occurr LAAM. Due to liver prolems ( minor) is being phased out Buprenorphine Not given orally Suboxone Combination of Bup plus Naloxone subligual Absorb the Bup, not the Naloxone If used IV then immediate Withdrawal from naloxone Practitioners need special DEA # and training Withdrawal treatment Methadone Buprenorphine Clonidine ++
  84. 84. -10 -9 -8 -7 -6 -5 -40102030405060708090100Intrinsic ActivityLog Dose of OpioidFull Agonist(Methadone)Partial Agonist(Buprenorphine)Antagonist (Naloxone)Intrinsic Activity: Full Agonist (Methadone), PartialAgonist (Buprenorphine), Antagonist (Naloxone)
  85. 85. Patient dependent on short-acting opioids?Withdrawal symptomspresent 12-24 hrsafter last use of opioids?Give buprenorphine2-4 mg, observe 2+ hrsWithdrawal symptomscontinue or return?Repeat dose up tomaximum 8 mg for first dayWithdrawal symptomsrelieved?Manage withdrawalsymptomaticallyYesYesNoStop;not dependenton short-actingopioidsNoYesYesFigure 3: Induction for Patient Physically DependentOn Short-acting Opioids, Day 1Withdrawal symptomsreturn?Daily dose established.GO TO SWITCHDIAGRAM (Fig. 6)No Daily dose established.GO TO SWITCHDIAGRAM (Fig. 6)NoReturn next day forcontinued induction.GO TO INDUCTION DAY 2DIAGRAM (Fig. 5)Yes
  86. 86. Benzodiazepines and other sedating drugsMedications metabolized by cytochromeP450 3A4Opioid antagonistsOpioid agonistsDrug Interactions with Buprenorphine
  87. 87. Drug Alcohol Depend. 2003 Apr1;69(3):263-72.Related Articles, LinksOpioid detoxification with buprenorphine, clonidine, or methadone inhospitalized heroin-dependent patients with HIV infection.Umbricht A, Hoover DR, Tucker MJ, Leslie JM, Chaisson RE, Preston KL.In a randomized, double-blind clinical trial, we evaluated the impact of three medications on the signs and symptoms ofwithdrawal and on the pain severity in heroin-dependent HIV-infected patients (N=55) hospitalized for medical reasons on aninpatient AIDS service. Patients received a 3-day pharmacologic taper with intramuscular buprenorphine (n=21), oral clonidine(n=16), or oral methadone (n=18), followed by a clonidine transdermal patch on the fourth day. Observed and self-reportedmeasures of opioid withdrawal and pain were taken 1-3 times daily for up to 4 days. Opiate administration used as medicallyindicated for pain was also recorded. Observer- and subject-rated opiate withdrawal scores decreased significantly followingthe first dose of medication and overall during treatment. Among all 55 subjects, self-reported and observer-reported paindecreased after treatment (on average observer-rated opioid withdrawal scale (OOWS) scores declined 5.6 units and shortopioid withdrawal scale (SOWS) declined 4.8 units, P<0.001, for both) with no indication of increased pain during medicatitaper.There were no significant differences of pain decline and other measures of withdrawal between the three treatmentgroups. During the intervention period, supplemental opiates were administered as medically indicated for pain to 45% of thepatients; only 34% of men versus 62% of women received morphine (P<0.05). These findings suggest buprenorphine,clonidine, and methadone regimens each decrease opioid withdrawal in medically ill HIV-infected patients.
  88. 88. Other Addiction Meds Relapse prevention…Alcohol Naltrexone…opiate system Acamprosate…GABA system??......... justreleased and being evaluated in large currentstudies
  89. 89. NALTREXONE IN THE TREATMENT OFALCOHOL DEPENDENCECumulative Relapse Rate00. 1 2 3 4 5 6 7 8 9 10 11 12No. of Weeks Receiving MedicationCumulativeProportionwithNoRelapseNaltrexone HCL (N=35)Placebo (N=35)Volpicelli et al., 1992
  90. 90. ACAMPROSATE RELAPSE RATES0102030405060708090100Acamprosate Placebo24 480 72 96Treatment Period Follow-up PeriodWeeks%ofAbstinentPatients
  91. 91. Addiction. 2004 Jul;99(7):811-28. Related Articles, LinksEfficacy and safety of naltrexone and acamprosate in the treatment ofalcohol dependence: a systematic review.Carmen B, Angeles M, Ana M, Maria AJ.Findings Thirty-three studies met the inclusion criteria.Acamprosate was associated with a significant improvement in abstinence rate [oddsratio (OR): 1.88 (1.57, 2.25), P < 0.001] and days of cumulative abstinence [WMD: 26.55(17.56, 36.54].Short-term administration of naltrexone reduced the relapse rate significantly [OR: 0.62(0.52, 0.75), P < 0.001], but was not associated with a significant modification in theabstinence rate [OR: 1.26 (0.97,1.64), P = 0.08].There were insufficient data to ascertain naltrexones efficacy over more prolonged periods.Acamprosate had a good safety pattern and was associated with a significantimprovement in treatment compliance [OR: 1.29 (1.13,1.47), P < 0.001]. Naltrexonesside effects were more numerous, yet the drug was nevertheless tolerated acceptablywithout being associated with a lower adherence to treatment (OR: 0.94 (0.80, 1.1), P = 0.5).However, overall compliance was relatively low with both medications.
  92. 92. Medications in Patients withAddictions….potential problems Can reinforce addiction denial if Alc/Drg intervention is notintegrated and supported…esp by the prescriber.. Can be expensive, cause side effects, could be used in overdose. Encumber the pt with seeing MD, or mental health system, cost,convenience etc….ie make sure they are really necessary. Active participation in recovery can be both antidep andantianx…but if serious psych problems continue, or disrupt recovery,meds should be considered For more serious problems such as psychosis and mania,immediate use of medications is indicated
  93. 93. Sleep in recovering Alc/Addicts Abnormal for weeks/months in most Is this “normal toxicity” and to betolerated Poor sleep associated with relapse, anx,dep, PTSD, and PROTRACTEDWITHDRAWAL
  94. 94. Medications for sleep in recoveringaddicts/alcoholics Treat the comorbid disorder causing the sleepproblem….ie dep/anx etc, with an antidepressant And/or protracted withdrawal…..with anticonvulsants (for one to several months) Prazosin for PTSD nightmares Anti histamines, trazedone, remeron as non-specific aids If using BZP‟s, oxazepam and librium
  95. 95. Anticonvulsants Role in alc withdrawal acute and/or protracted Role in bipolar, esp rapid cycle Role in early antipsychotic augmentation Great for ongoing sleep problems... Is this protractedwithdrawal? Is there a role in craving/relapse prevention? Is there a role for PRN use in agitated Dual pts, such as500 mg valproate, 600 mg gabapentin etc??
  96. 96. Anticonvulsants in alcoholwithdrawal Good evidence for carbamazepine, valproate andgrowing for gabapentin and topiramate May even be superior in terms of safety, ability for takehome doses and in some studies, even anxiety/agitation Have been shown effective in high dose BZP dependence
  97. 97. Stay Cool andKeep Calm