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Pharmacology Update CEBP Conference 2012 October 22 and 23, 2012 Chris4na M. Delos Reyes, MD Medical Consultant, Center for EBPs at Case Chief Clinical Officer, ADAMHS Board Cuyahoga County Associate Professor, UHCMC Dept of Psychiatry 1
www.centerforebp.case.edu
www.centerforebp.case.edu
Learning ObjecGves •  1. List newly‐approved medicaGons for the treatment of severe mental illness and substance use disorders. •  2. Discuss common interacGons between psychiatric medicaGons and substances of abuse. •  3. IdenGfy strategies to increase medicaGon non‐adherence and to decrease substance use in paGents with dual disorders. 5
General Guidelines for Psychopharmacology of Dual Disorders •  Determine mental illness and substance abuse diagnosis –  Avoid treaGng substance induced symptoms –  Do not withhold meds in presence of substance abuse •  Use meds with low abuse potenGal –  Avoid creaGng new addicGons (benzo & sGm) •  Use meds with low lethality –  High prevalence of overdose in dual disorders –  Avoid tricyclics, MAO‐I, toxic combinaGons 6
General Guidelines (conGnued) •  Consider selecGng med that also reduces craving or substance use (SSRI, Clozapine) •  Consider prescribing meds specific for the treatment of addicGon (naltrexone, disulfiram) •  Dispense limited amounts •  Monitor closely for response 7
Psychotropic MedicaGons • 
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Mechanism of acGon IndicaGons and therapeuGc effects Adverse effects Common side effects 8
AnGdepressants •  SSRIs: Prozac, ZoloY, Celexa, Lexapro, Paxil, Luvox •  SNRIs: Effexor, Cymbalta, PrisGq •  TCAs: amitriptyline, doxepin, desipramine, nortriptyline, imipramine, and several others •  MAOIs: Nardil, Parnate •  Other anGdepressants: Wellbutrin, Remeron, Trazodone, Serzone 9
AnGdepressants: Mechanism •  Most work by increasing the amount of neurotransmi_ers in the brain •  Common neurotransmi_ers that regulate mood: –  Serotonin –  Norepinephrine –  Dopamine 10
AnGdepressants: IndicaGons •  Major Depression •  Bipolar Disorder, depressed phase –  Use in combinaGon with mood stabilizer • 
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Panic Disorder Obsessive‐Compulsive Disorder PTSD Social Phobia GAD Smoking CessaGon (Wellbutrin) Others: Bulimia, PMDD 11
AnGdepressants: Adverse Effects •  SSRIs: generally very safe; “SSRI withdrawal” •  SNRIs: Effexor may increase diastolic BP •  TCAs: may be lethal in overdose in small amounts, cardiac toxicity, anGcholinergic toxicity •  MAOIs: adrenergic crisis when dietary amines ingested, serotonin syndrome when mixed w/ SSRIs 12
AnGdepressants: Adverse Effects •  Wellbutrin: ↑ seizure risk in doses over 450mg •  Trazodone: priapism •  Serzone: liver failure 13
AnGdepressants: Common Side Effects •  SSRIs: nausea, sweaGng, headache, insomnia, sedaGon, ji_eriness, dizziness, sexual dysfxn. •  SNRIs: nausea, sedaGon, insomnia, dizziness •  TCAs: dry mouth, blurred vision, consGpaGon, sedaGon, hypotension, tachycardia, urinary hesitancy •  MAOIs: hypotension, insomnia, agitaGon, sedaGon, sexual dysfxn, dry mouth, consGpaGon, peripheral neuropathies 14
AnGdepressants: Common Side Effects •  Wellbutrin: headache, dry mouth, agitaGon, weight loss, insomnia, consGpaGon, tremor •  Remeron: sedaGon, weight gain, dry mouth, consGpaGon, hypotension •  Trazodone: sedaGon, hypotension, headache •  Serzone: sedaGon, dizziness, dry mouth, nausea, consGpaGon, blurred vision, headache 15
ConvenGonal AnGpsychoGcs •  Most work by blocking dopamine (D2) receptors •  Indicated for the treatment of psychoGc disorders, including –  schizophrenia –  schizoaffecGve disorder –  bipolar disorder, acute mania or psychosis –  major depression with psychoGc features 16
ConvenGonal AnGpsychoGcs •  Moderate Potency: •  High Potency: –  Haldol –  Prolixin –  Stelazine –  Navane –  Orap –  Loxitane –  Moban –  Trilafon •  Low Potency: –  Thorazine –  Mellaril –  SerenGl 17
Conv. AnGpsychoGcs: Adverse Effects •  NMS: neurolepGc malignant syndrome –  PotenGally lethal; includes hyperthermia, autonomic instability, sweaGng, confusion, elevated CK, rigidity, fluctuaGng consciousness •  Tardive dyskinesia –  Late‐developing involuntary movement disorder, common in mouth, tongue, upper extremiGes 18
Conv. AnGpsychoGcs: Adverse Effects •  Dystonia –  Extremely uncomfortable involuntary muscle spasm; may be life‐threatening if it occurs in the larynx •  HyperprolacGnemia –  Associated with amenorrhea, galactorrhea, and sexual dysfuncGon 19
Conv. AnGpsychoGcs: Common Side Effects •  High Potency meds: •  Dystonia –  Muscle spasms •  Akathisia –  Motor restlessness •  Parkinsonism –  Rigidity –  Tremor –  Bradykinesia • 
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Low Potency meds: SedaGon Hypotension Weight gain AnGcholinergic s/e –  Dry mouth –  Blurred vision –  ConsGpaGon –  Urinary retenGon 20
Novel AnGpsychoGcs •  “SGAs”: second‐generaGon anGpsychoGcs •  Block D2 receptors, but also block serotonin receptors •  Advantages over convenGonal anGpsychoGcs –  Decreased EPS and li_le/no prolacGn elevaGon; may be be_er for negaGve symptoms •  Clozapine: only med clearly more effecGve than all others for psychosis (esp. treatment resistant schizophrenia) 21
Novel AnGpsychoGcs • 
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Clozapine =
Risperidone =
Olanzapine =
QueGapine =
Ziprasidone =
Aripiprazole =
Paliperidone =
Asenapine =
Iloperidone =
Lurasidone =
Clozaril Risperdal Zyprexa Seroquel Geodon Abilify Invega Saphris Fanapt Latuda 22
Clozapine (Clozaril) •  Used for treatment‐resistant psychosis •  Adverse effects: –  Agranulocytosis in 1.6% of paGents—must check WBC regularly –  Dose‐related seizures •  Side effects: sedaGon, tachycardia,weight gain, hypersalivaGon, dizziness, consGpaGon, nausea, headache, hypotension, diabetes 23
Risperidone (Risperdal) •  May be more effecGve for (‐) sx vs. convenGonal meds •  Does cause EPS (>6mg) and ↑ prolacGn •  Side effects: dizziness, hypotension, headache, nausea, vomiGng, anxiety, rhiniGs, coughing, weight gain, QT prolongaGon •  Injectable form (Q 2 wks) “Risperdal Consta” (doses: 12.5, 25, 37.5, 50) 24
Olanzapine (Zyprexa) •  Most closely resembles clozapine •  Also has anGmanic and anGdepressant effect vs. placebo •  Adverse effects: new‐onset diabetes and diabeGc ketoacidosis •  Side effects: sedaGon, weight gain, consGpaGon, dry mouth, dizziness, elevaGon of SGPT •  Injectable form (Q2‐4 weeks) “Zyprexa Relprevv” (doses: 150, 210, 300, 405) 25
QueGapine (Seroquel) •  Blocks dopamine, serotonin, alpha‐adrenergic receptors •  Usually requires mulGple daily doses •  Adverse effects: cataracts (in beagles); ? Risk in humans •  Side effects: hypotension, sedaGon, elevated LFTs, decreased T3 and T4, weight gain 26
Ziprasidone (Geodon) Blocks more serotonin than dopamine Must be given twice daily with food May cause less weight gain vs. others Adverse effects: causes QTc increase on EKG; cauGon in those with cardiac disease, low K or low Mg •  Side effects: nausea, sedaGon vs. acGvaGon, dizziness, hypotension •  Short‐acGng injecGon available • 
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Aripiprazole (Abilify) •  ParGal agonist at D2 and serotonin 1A receptors; blocks serotonin 2A receptors •  “dopamine‐serotonin system stabilizer” •  Side effects: nausea, vomiGng, anxiety, headache, sedaGon, hypotension, tachycardia, insomnia, akathisia, EPS, weight gain 28
Paliperidone (Invega) •  The primary acGve metabolite of risperidone •  Usual dose 6mg daily, max dose 12 mg daily •  PotenGal for GI obstrucGon –  PaGent may noGce tablet‐shaped “shell” in stool •  Injectable form: “Invega Sustenna” (Q4 weeks) •  Most common side effects: –  extrapyramidal symptoms, tachycardia, akathisia, somnolence, dyspepsia, consGpaGon, weight increased, and nasopharyngiGts Asenapine (Saphris) •  Blocks serotonin 2A, dopamine 2, alpha‐
adrenergic, and histamine receptors •  Fast‐dissolving sublingual form (5 &10 mg) •  Approved for both Schizophrenia and Bipolar I •  Most common side effects: –  somnolence/sedaGon/hypersomnia (23%), dizziness (10%), EPS other than akathisia (7%), akathisia (5%) oral hypoesthesia (5%) and weight increased (5%) Iloperidone (Fanapt) •  Blocks D2, D3, 5HT1a, alpha1 and alpha2c receptors; low affinity for histamine; no affinity for muscarinic receptors •  Approved for schizophrenia—6 to 12mg twice daily, max dose 24mg daily •  Metabolized by CYP2D6 and CYP3A4 •  Can increase QTc •  Most common side effects: –  Dizziness (20%), Somnolence (15%), Tachycardia (12%), Nausea (10%), Dry mouth (10%), Weight gain (9%) Lurasidone (Latuda) •  Blocks D2, 5HT2a, alpha 2a and 2c; parGal agonist at 5HT1a; li_le affinity for histamine and muscarinic receptors •  Approved for Schizophrenia—usual dose 40mg daily, max dose 80mg daily •  Cannot use with CYP3A4 inducers/inhibitors •  Most common side effects –  Somnolence (22%), Akathisia (15%), Nausea (12%), Parkinsonism (11%), VomiGng (8%), Insomnia (8%) Mood Stabilizers •  Before 2002, only 2 FDA‐approved drugs for bipolar disorder •  Novel anGpsychoGcs are also approved for Bipolar Disorder •  Many other drugs are used off‐label –  Many (not all) are also anGconvulsants •  Also used to treat sx of schizoaffecGve disorder, anxiety disorders, aggressive behavior, etc. 33
Mood Stabilizers •  FDA Approved: •  Not yet approved: •  Lithium •  Valproic Acid •  Lamotrigine • 
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Carbamazepine GabapenGn Topiramate Tiagabine Oxcarbazepine 34
Lithium Naturally occurring caGon Blocks G‐proteins and PIP (post‐synapGcally) Aim for blood levels of 0.6‐1.2 mEq/L Adverse effects: hypothyroidism, renal effects, cardiac effects, teratogenic, lithium toxicity •  Side effects: sedaGon, decreased cogniGon or creaGvity, dry mouth, hand tremor, weight gain, polydipsia/polyuria, nausea, diarrhea • 
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Valproic Acid •  Depakene and Depakote (divalproex sodium) •  Increases brain levels of GABA •  Blood levels of 50‐100 mcg/mL are therapeuGc in seizures •  Adverse effects: hepatotoxicity, pancreaGGs, aplasGc anemia, increase in LFTs, teratogenic •  Side effects: n/v/d, sedaGon, dizziness, tremor, weight gain, alopecia, ataxia, heartburn 36
Lamotrigine •  AnGconvulsant approved for Bipolar disorder –  May be helpful during depressed phase •  Blocks glutamate & voltage‐gated Na channels •  Adverse effects: severe rash, may lead to Stevens‐Johnson syndrome; cauGon when mixing with valproic acid •  Side effects: benign rash, headache, blurred vision, ataxia, dizziness, nausea, faGgue 37
Carbamazepine •  Blocks sodium channels –  Both voltage‐gated and pre‐synapGc •  Induces its own metabolism: must increase dose aYer 2‐3 weeks –  Lowers levels of many meds (BCP, anGpsychoGcs) •  Adverse effects: aplasGc anemia, hepaGGs (both are rare but potenGally fatal), teratogenic •  Side effects: dizziness, ataxia, sedaGon, dysarthria, nausea, rash, low sodium 38
AnxiolyGcs •  Many SSRIs treat anxiety disorders •  Other classes of meds include benzodiazepines and buspirone •  Benzodiazepines acGvate the GABA‐A receptor complex •  Buspirone is a parGal agonist at the serotonin 1A receptor 39
Benzodiazepines •  Large class of meds, usually listed by half‐life –  Long: Valium, Klonopin, etc. –  Moderate: AGvan, Serax, etc. –  Short: Xanax, Halcion, etc. •  Adverse effects: tolerance, dependence, withdrawal if suddenly stopped, memory impairment, ? Teratogenic •  Side effects: sedaGon, ataxia, dizziness 40
Buspirone • 
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Not effecGve for panic disorder, used for GAD Delayed onset (2‐4 wks) vs. benzodiazepines Does not cause dependence or withdrawal Side effects: dizziness, nausea, headache, nervousness 41
HypnoGcs: The “Z‐drugs” •  Non‐Benzodiazepine drugs that are used to treat insomnia; they act like benzodiazepines •  NOTE: they are sGll controlled substances and have addicGve potenGal •  Zolpidem—Ambien •  Zaleplon—Sonata •  Zopiclone—Imovane (not available in US) •  Eszopiclone‐‐Lunesta Psychotropic MedicaGons •  Risks and InteracGons to consider when prescribing for clients with dual disorders 43
PotenGal Risks and InteracGons in Clients With Dual Disorders AnGdepressant MedicaGons •  Tricyclic anGdepressants –  Chronic alcohol use may induce metabolism and decrease levels –  AddiGve cardiotoxicity with cocaine 44
PotenGal Risks and InteracGons in Clients With Dual Disorders AnGdepressant MedicaGons (conGnued) •  MAO Inhibitors –  Tyramine present in alcoholic beverages may produce elevated blood pressure – hypertensive crisis –  PotenGaGon of sympathomimeGc effects of sGmulants – hypertension/hyperpyrexia –  Toxic interacGon with meperidine (hypertensive crisis) 45
PotenGal Risks and InteracGons in Clients With Dual Disorders •  SSRIs –  Possibly lower seizure threshold •  Other anGdepressants –  Alcohol or benzodiazepines increase cogniGve and motor side effects of mirtazapine –  Venlafaxine elevates blood pressure, as does alcohol use and withdrawal –  Bupropion lowers seizure threshold which could increase risk of seizure with cocaine use or alcohol withdrawal 46
PotenGal Risks and InteracGons in Clients With Dual Disorders AnGpsychoGc MedicaGons •  ConvenGonal –  Possible increased risk of dystonia, akathisia, and tardive dyskinesia –  Risk for hyperpyrexia in combinaGon with sGmulants –  Cigare_e smoking lowers blood levels 47
PotenGal Risks and InteracGons in Clients With Dual Disorders AnGpsychoGc MedicaGons (conGnued) •  Novel (Atypical) –  Risk of respiratory suppression with combinaGon of clozapine and benzodiazapines –  Alcohol may synergisGcally increase sedaGve effects of clozapine –  Clozapine lowers seizure threshold 48
PotenGal Risks and InteracGons in Clients With Dual Disorders Mood Stabilizers •  Lithium –  Specific interacGons not documented •  Valproic acid –  PotenGal for liver toxicity •  Carbamazepine –  PotenGal for liver toxicity 49
PotenGal Risks and InteracGons in Clients With Dual Disorders AnxiolyGcs •  Benzodiazapines –  SubstanGal abuse potenGal •  Buspirone –  Specific interacGons not documented 50
PotenGal Risks and InteracGons in Clients With Dual Disorders SGmulants –  Possible abuse potenGal AnGparkinsonian MedicaGons –  Possible abuse potenGal 51
Summary –  Use novel anGpsychoGcs and newer anGdepressants •  Safer, reduce negaGve and cogniGve symptoms •  Enhance rehabilitaGon efforts –  Avoid benzodiazepines, sGmulants, anGcholinergics in acGve substance abusers –  Educate paGents and families •  Benefits of taking meds •  Risks of substance use in conjuncGon with meds –  In general: do not withhold psychotropics in paGents with substance use disorders 52
MedicaGons to treat Substance Dependence •  Alcohol dependence – Disulfiram, acamprosate, naltrexone, topamax •  Opiate dependence – Naltrexone, methadone, buprenorphine •  NicoGne dependence – NRT, buproprion, varenicline, etc •  Other drug dependence? 53
Disulfiram •  Inhibits metabolism of ETOH (Alcohol dehydrogenase) •  Acetaldehyde accumulates and causes “hangover” HA, flush, malaise, nausea, vomiGng, increased blood pressure •  Risk for heptatotoxicity –  Monitor liver enzymes 54
Disulfiram •  Supervised administraGon 125‐500 mg/day –  Clinician or family 2‐5 days/week • 
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Decrease alcohol use by deterring impulsive drinking May need to raise dose to elevate effect Reports of increased psychoGc symptoms (rare) Educate, informed consent Appropriate in acGon stage treatment with moGvated clients 55
Acamprosate •  A syntheGc taurine derivaGve with a structural resemblance to gamma amino‐butyric acid (GABA) •  Re‐calibrates the GABA and glutamate neurotransmi_er systems •  Recommend absGnence at start of treatment •  May reduce sx of post‐acute withdrawal –  Insomnia, anxiety, restlessness, dysphoria 56
Acamprosate •  Recommended dose: 666 mg three Gmes a day •  Renal excreGon; few drug‐drug interacGons •  Reduce dose in those with renal impairment •  Well‐tolerated with disconGnuaGon rate similar to placebo –  Diarrhea, dose‐related and transient, is most common side effect •  Safe in overdose •  Teratogenic in animals 57
Acamprosate: Recent Research •  2004: European meta‐analysis of 17 clinical trials showed 36% conGnuous absGnence at 6 months (vs. 23% who took placebo) •  2006: Two large U.S. trials failed to confirm efficacy •  Why the discrepancy? –  More severe alcohol dependence in European trials –  European paGents had been absGnent longer than paGents in U.S. trials 58
Naltrexone •  Blocks opioid receptors that are involved in the rewarding effects of drinking alcohol and alcohol craving •  Blocks effect of opiates –  May precipitate opiate withdrawal in abusers •  Risk for hepatotoxicity –  Monitor for liver enzymes 59
Naltrexone •  Efficacy highest in paGents who can abstain for 4 to 7 days before iniGaGng treatment •  No negaGve effect with use •  Some clients noGce anxiolyGc effect 60
Long‐ AcGng Naltrexone •  Given monthly, 380 mg appears to have increased efficacy versus 190 mg •  May have increased efficacy for men vs. women, and those absGnent when medicaGon is iniGated vs. those sGll drinking 61
Long‐ AcGng Naltrexone •  DisconGnuaGon rate‐ 14% in paGents on 380 mg a month, 7% in paGents on 190 mg a month and placebo. Most common side effects: nausea, injecGon site reacGon, headache. •  LFTs remained stable throughout the medicaGon trial 62
Naltrexone: Recent Research •  2005: Cuts the relapse risk during first 90 days by 36% (28% relapse rate on oral naltrexone vs. 43% relapse rate on placebo) •  2005: injectable naltrexone resulted in a 25% reducGon in proporGon of heavy drinking days vs. placebo •  Overall: helps to curb consumpGon in paGents with mulGple “slips” but less effecGve in maintaining absGnence 63
Topiramate •  NOTE: unlike acamprosate, disulfiram, and naltrexone, topiramate is not FDA‐approved for alcoholism –  Approved for treatment of seizure disorders •  ↑ GABA and ↓ glutamate transmission –  Precise mechanism of acGon is unclear •  Requires slow upward GtraGon •  Efficacy has been established in individuals who were sGll drinking at the Gme of starGng the medicaGon 64
Topiramate: Recent Research •  2 Randomized Controlled Trials (RCTs) showed significant increase in proporGon of individuals with 28 consecuGve days of absGnence (2003, 2007) •  Magnitude of the effect may be larger than that for naltrexone and acamprosate (!) 65
Other Agents to Reduce Drinking •  Nalmefene (opiate antagonist) – Reduces alcohol relapses; ↓ liver toxicity vs. naltrexone (no pill form available yet) •  Ondansetron (5HT‐3 antagonist) –  Reduced days of drinking for early onset alcoholism 66
Naltrexone •  Opiate antagonist to treat opiate dependence •  All effects of opiates are blocked –  Must be detoxed and opiate‐free or else will cause opiate withdrawal syndrome •  Non‐compliance is the main barrier to success •  Most useful for highly moGvated paGents w/ external circumstances –  Impaired professionals, parolees, probaGoners, etc 67
Methadone •  Opiate agonist to treat opiate dependence •  Well‐studied and effecGve treatment –  Normalizes funcGon/return to work, decreases crime/violence, reduces HIV exposure •  Doses > 70mg/day generally be_er than low doses •  Enhanced services = improved outcomes –  Counseling, medical, social/vocaGonal services,etc •  No contraindicaGon in SMI, though not well studied 68
Buprenorphine   Opioid parGal agonist   ↓ risk of overdose and ↓ abuse potenGal   May precipitate opiate withdrawal in dependent individuals   Approved for treatment of opiate dependence –  Maintenance dose in the range of 8‐16 mg daily   Sublingual route of administraGon   Subutex= Bup only; Suboxone= Bup + Naloxone   Suboxone Sublingual Film (Sept 2010 release) 69
Buprenorphine •  Approved in U.S. (2002) as office‐based treatment vs. ‘methadone clinics’ •  Individual doctors may treat up to 30 paGents at a Gme, using an special DEA # –  AYer 1 year, may increase to 100 paGents •  Must be addicGon medicine/addicGon psychiatry cerGfied OR complete 8‐hr training 70
Buprenorphine: Recent Research •  The SAMHSA EvaluaGon of the Impact of the DATA Waiver Program –  FINAL REPORT in March 2006 •  Buprenorphine clinically effecGve and well accepted by paGents. •  Waiver Program has ↑ the availability of medicaGon‐assisted treatment for opioid addicGon. •  Adverse effects, whether involving diversion or adverse clinical events or public health consequences, have been minimal. •  The 30‐paGent limit on individual physician pracGces and cost / reimbursement issues may be decreasing potenGal access to treatment. •  For more informaGon, see www.buprenorphine.samhsa.gov 71
NicoGne Replacement Therapy (NRT)‐ General Issues •  Recent pracGce guidelines have advised the use of NRT for all paGents a_empGng to stop smoking •  Studies have consistently demonstrated that the addiGon of NRT to behavioral intervenGons doubles the quit rates •  NicoGne replacement products: gum (prescripGon, OTC), patch (prescripGon, OTC), nasal spray (prescripGon only), inhaler (prescripGon only) 72
NRT‐ NicoGne Patch •  Number of cigare_es smoked per day can be used to guide patch dosing Cigare_es/day Patch dose (mg/day) <10
7‐14 10‐20 14‐21 21‐40 22‐44 >40
44+ 73
Non‐NicoGne Products for Smoking CessaGon •  Bupropion •  Nortriptyline •  Clonidine •  CombinaGon treatments NRT + Bupropion NRT + Naltrexone 74
Buproprion •  Marketed as anGdepressant (Wellbutrin) and as smoking cessaGon aid (Zyban) •  Use at 300mg dose to help with smoking cessaGon •  May be more effecGve in combinaGon with nicoGne replacement •  Common side effects: headache, dry mouth, insomnia, acGvaGon, weight loss 75
Non‐ NicoGne Products for Smoking CessaGon (2) •  Varenicline (parGal nicoGnic receptor agonist) –  May be as efficacious or slightly more efficacious versus bupropion in leading to sustained cessaGon •  Rimonabant (cannabinoid receptor antagonist) –  May promote less weight gain in qui_ers   Vaccine (NicVAX)   Hatsukami, et al‐ Clin Pharmacol Ther 2005;78:456‐467 76
ChanGx (varenicline) •  ParGal agonist at the Alpha‐4,Beta‐2 neuronal nicoGnic acetylcholine receptor •  Start medicaGon 1 week before the quit date –  Day 1 to 3 take 0.5mg daily –  Day 4 to 7 take 0.5mg twice a day –  Day 8 to end of tx take 1mg twice a day •  Take aYer eaGng and with 8 oz. of water •  Usually take for 12 weeks, but some make take for an addiGonal 12 weeks 77
ChanGx (varenicline) •  Common side effects: nausea, sleep disturbance, consGpaGon, gas, vomiGng •  If on dialysis or have kidney problems, may need to reduce the dose •  Has not been studied in pregnant or breas~eeding women 78
ChanGx: Recent Research •  May 2006: FDA approves ChanGx •  November 2007: FDA Early CommunicaGon –  adverse event reports on ChanGx related to changes in behavior, agitaGon, depressed mood, suicidal thoughts, and a_empted and completed suicide. •  February 2008: FDA Public Health Advisory –  Tell your health care provider about any history of psychiatric illness before you start taking ChanGx. –  Immediately tell a doctor if you or someone you care for has any changes in mood and behavior while being treated with ChanGx 79
Cocaine Use Disorders‐ Pharmacotherapies (1) •  Agents possibly useful in withdrawal phase (None FDA approved) – AmanGdine‐ indirect Dopamine (DA) agonist – Propranolol‐ ß‐ blocker Psychiatric Times, Feb 2005. Vol 22, #2, Kampman p
38-46
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Cocaine Use Disorders‐ Pharmacotherapies (2)  Agents possibly useful in relapse prevenGon (None FDA approved) – GABAergic Agents •  Baclofen‐ GABA‐ B agonist •  Topiramate‐ facilitates GABA neurotransmission, inhibits glutamate neurotransmission •  Tiagabine‐ selecGve blocker of GABA reuptake transporter – Disulfiram‐ blocks enzymaGc degradaGon of cocaine and DA 81
Cocaine Use Disorders‐ Pharmacotherapies (3)  Agents possibly useful in relapse prevenGon (cont.) –  Modafanil‐ enhances glutamate neurotransmission, reduces cocaine craving and may block cocaine‐ induced euphoria. NIH/ NIDA clinical trials in progress (Spring 2006) –  Vaccine (TA‐CD)‐ human trials promising, need to produce minimum anGbody level for efficacy in reducing cocaine self‐ administraGon. Human trials have used a series of three vaccinaGons.
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Rimonabant and Marijuana Dependence? •  Rimonabant (Acomplia) available in Europe and S.A. •  Process in US (for ZimulG) has been stalled due to concerns re: severe psychiatric side effects •  CB1 and CB2 are 2 known cannabinoid receptors –  Rimonabant is a selecGve CB1‐A endocannabinoid receptor antagonist indicated for the treatment of obesity •  ??—Use in marijuana dependence –  THC and anandamide acGvate these receptors, increasing appeGte (marijuana “munchies”) 83
Med Non‐adherence •  Assess and adjust for adherence •  Monitor dose‐taking •  Consider med interacGons, alcohol and cigare_es •  Retest for medicaGon blood levels 84
Med Non‐adherence (conGnued) •  Does the client understand the benefits of taking medicaGon? •  Does the client believe that taking medicaGon will help him or her make progress towards achieving personally desired goals? •  Are there bothersome side effects that need to be addressed? •  Does the client misa_ribute certain problems or symptoms to the medicaGon that may be due to other causes? 85
Med Non‐adherence (conGnued) •  Is the client afraid of specific interacGons between medicaGon and substances of abuse, leading to non‐
adherence when using substances? •  Does the client need a helpful prompt to overcome forge~ulness or disorganizaGon? •  Can taking medicaGon regularly be fit into the client’s daily rouGne? •  Is the medicaGon regimen unnecessarily complicated? 86
Hope for Recovery •  People with dual disorders oYen lack experiences of success and have lost hope •  MedicaGons in conjuncGon with other intervenGons can increase hope for a be_er life –  Via reducGon in bothersome symptoms •  Target clients’ complaints + psychiatric symptoms –  Via reduced craving for substances –  Via support for sobriety 87
Summary •  Prescribing principles guide pracGce for paGents with dual disorders •  All SAMI providers need to be familiar with: –  Strategies to decrease medicaGon non‐adherence –  DetoxificaGon guidelines –  MedicaGon side effects and alcohol/drug interacGons –  MedicaGons helpful in treaGng addicGon 88
Resources •  Mary Brune_e, MD of Dartmouth Psychiatric Research Center •  Mueser et al., Integrated Treatment for Dual Disorders: A Guide to EffecAve PracAce. New York: Guilford Press, 2003. •  Sofuoglu M, Kosten TR. Pharmacologic management of relapse prevenGon in addicGve disorders. Psychiatr Clin N Am 27:627‐648, 2004. •  Mid‐America AddicGon Technology Transfer Center. PsychotherapeuAc MedicaAons 2011: What Every Counselor Should Know. h_p://www.ma_c.org 89
www.centerforebp.case.edu
www.centerforebp.case.edu
Contact InformaGon ChrisGna M. Delos Reyes, MD Medical Consultant Center for Evidence‐Based PracGces at Case Website: www.centerforebp.case.edu Voicemail: 216‐844‐7661 Email: [email protected]