IPAP Cocaine Dependence Algorithm

Transcription

1 IPAP Cocaine Dependence Algorithm page 1 of 7

2 Overall context and level of evidence When selecting pharmacotherapies for stimulant dependence, one must keep in mind that there are no medications that have been shown to be consistently effective for its treatment in Phase III trials. Therefore, no medications have been approved by the FDA in the United States or have achieved equivalent approval from any other government in the world. The studies used to support the usefulness of the medications included in the algorithm were relatively small, and in some cases, were only pilot trials. All of these studies need to be replicated in large-scale controlled clinical trials. Therefore, the research status report in this algorithm must be considered tentative and inconclusive, and does not reflect a set of clinical recommendations. Although this algorithm focuses on cocaine dependence, the same conclusions can be drawn regarding the pharmacological treatment of methamphetamine dependence: there is no reliable evidence for the efficacy of any medication for the treatment of this patient population. A number of different agents have been tested, including sertraline, bupropion, ondansetron, imipramine, baclofen, and gabapentin; none of these agents have been demonstrated effective in this population. Psychosocial treatment remains the mainstay of treatment for stimulant dependence, and none of the medications discussed in the algorithm should be considered a replacement for psychosocial treatment; rather medications may sometimes serve as a helpful adjunct to psychosocial treatment. Cocaine intoxication, psychosis and agitation Stimulant-induced psychosis consists of paranoid delusions and various forms of hallucinations 1. It is usually brief, in most cases lasting only a few hours with cocaine but up to a day or sometimes considerably longer with methamphetamine. It may be treated with support and monitoring or may be treated with brief courses of antipsychotics 1. Cocaine intoxication may also result in agitation. This is usually best controlled with a benzodiazepine 2. Beta blockers, especially propranolol, are best avoided in the acute treatment of cocaine intoxication. Beta adrenergic stimulation results in coronary artery vasodilatation, whereas alpha adrenergic stimulation tends to cause vasoconstriction. Therefore isolated beta adrenergic blockade without concurrent alpha blockade may result in coronary artery vasoconstriction due to unopposed alpha adrenergic stimulation. The use of propranolol longer term should be reserved for patients without a history of coronary artery disease who have not experienced cocaine-induced chest pain 3. Psychosocial treatment Medications for the treatment of any substance abuse disorder should be given in the context of some form of psychosocial treatment. For cocaine dependence, psychosocial treatments including 12-step oriented individual drug counseling, cognitive behavior therapy and contingency management have been shown to be effective 4-6. Cocainedependent individuals who actively participate in self-help groups such as Alcoholics Anonymous and Narcotics Anonymous appear to have better drug use outcomes than those who do not do so 7. Double-blind, placebo-controlled trials have shown an interaction between contingency management, in the form of vouchers given for demonstrated cocaine abstinence, and antidepressant medications including desipramine and bupropion 8, 9 ; the use of contingency management appears to enhance the effects of these medications. Notes on the Algorithm Nodes Node C1. Making the diagnosis of cocaine dependence Trials conducted to date with pharmacotherapies for cocaine dependence have utilized patients with the cocaine dependence, usually using criteria for the Diagnostic and Statistical Manual published by the American Psychiatric Association. In making an initial assessment of an individual with a substance use problem, it is important to establish the presence of cocaine dependence and all other substance use disorders and co-occurring psychiatric illnesses, both of which are quite common among those with cocaine dependence (see Node CC). The accompanying psychiatric illness may complicate the treatment of the cocaine dependence and may suggest other pharmacological approaches. At the same time the patient should be assessed with regard to the following considerations. These should be reassessed throughout the treatment. page 2 of 7

3 Node CA. Cocaine dependence occurs frequently with other substance use disorders. Therefore, when diagnosing cocaine dependence, it is useful to ask about use of other substances of abuse. Node CB. Medical problems are very common in individuals with cocaine dependence. These include local problems (e.g., nasal mucosal ulcers, crack lung ) resulting from cocaine s vasoconstrictor properties, as well as cardiovascular complications resulting from its sympathomimetic properties. A medical assessment should thus be performed in this population. Node CC. Other psychiatric disorders (e.g. mood disorders) frequently occur in patients with cocaine dependence, and the co-occurrence of cocaine dependence can affect treatment response to pharmacotherapy for other psychiatric illness. For instance, major depressive disorder is often seen in cocaine-dependent patients. Clinical trial evidence suggests that tricyclic antidepressants may be more effective than SSRIs for controlling depressive symptoms in cocaine-dependent patients with major depression. However, their usefulness may be limited by side effects 10, 11. No antidepressant, on the other hand, has been shown to be superior to placebo in reducing cocaine use in depressed cocaine dependent patients in a clinical trial. For patients with bipolar disorder and cocaine dependence, very little is known regarding the relative effectiveness of mood stabilizers in this population. Although open-label pilot trials suggest that divalproex and lamotrigine may be effective in controlling cocaine use as well as mood symptoms 12, 13, confirmation by double-blind placebo-controlled trials does not exist. Among patients with co-occurring cocaine dependence and schizophrenia, small trials suggest that antipsychotic treatment resulted in improved outcome. However, superiority of atypical antipsychotics over traditional antipsychotics has not been established and no particular antipsychotic medication has been shown to be consistently more efficacious than another in this patient population Treatment of cocaine-dependent patients with adult attention deficit hyperactivity disorder (ADHD) has been studied. A trial comparing sustained-release methylphenidate to placebo did not show differences between the two groups in either ADHD symptoms or cocaine abstinence 18. The use of stimulant medications in individuals who have abused stimulants is controversial, however, and carries the risk of abuse of the medication as well. Prescription of abusable medications to individuals with a substance abuse history should be done with great caution, after thorough weighing of risks and benefits, and careful monitoring of prescriptions and refills. Node CD. Patients with cocaine dependence are at significantly greater risk of suicide than those without this disorder. An assessment for suicidal risk is thus useful in this population. Node CE. None of the medications listed in this algorithm are FDA-approved for cocaine dependence treatment. They should thus not be used for this purpose in pregnant women. Node CF. Poor adherence to treatment could result from side effects, poor initial results, or ambivalence about quitting. Adherence should be regularly assessed. Depending on the reason for non-adherence, one should consider instituting more intensive counseling or perhaps adjusting the medication regimen. Node CG. Patients who have low motivation for change frequently do not return for treatment. Indeed, chronic stimulant use may create dysfunction in the dopamine-mediated reward system, creating a situation in which stimulant-dependent individuals may be relatively unmotivated by normal life rewards. Counseling approaches that use motivational interviewing techniques (including educating patients that some of their lack of motivation may be drug-induced) can be tried to enhance willingness for treatment. Sometimes, the legal system or significant others may help to provide external motivation while waiting for internal motivation to be bolstered. More intensive psychosocial interventions, including intensive outpatient programs or residential treatment, should be considered to help patients engage in the treatment process. Node CH. Cocaine-dependent individuals may experience legal problems, and may in fact be seeking treatment as a result of these problems. This type of external motivating influence can sometimes be helpful in precipitating changes in drug use for this population. Node C2. Evaluate for most recent cocaine use, presence of cocaine withdrawal, and co-occurring substance use disorders. Although cocaine withdrawal is not medically significant, the presence of recent cocaine use and the presence of more severe cocaine withdrawal symptoms predicts a poorer response to treatment and may predict patient response to certain medications If co-occurring alcohol or opioid, or sedative-hypnotic dependence are diagnosed, it is necessary to page 3 of 7

4 ensure that safe and appropriate medical detoxification is carried out, if necessary. In the case of opioid dependence, treatment with an agonist (eg, methadone) or partial agonist (eg, buprenorphine) may be attempted to assist in detoxification, or as agonist treatment in lieu of detoxification. The presence or absence of alcohol dependence may also affect choice of medication for the treatment of cocaine dependence. Node C3. Patients with recent cocaine use and more severe cocaine withdrawal symptoms Patients with more severe cocaine withdrawal symptoms may respond better to medications that are able to address cocaine withdrawal symptoms, e.g., propranolol or modafinil. Propranolol has been shown to improve treatment retention and reduce cocaine use among cocaine -dependent patients with more severe cocaine withdrawal symptoms 22, 23. The dose of propranolol used is relatively low: 100 mg daily divided into three daily doses (40 mg /20 mg /40 mg). The effectiveness of propranolol is extremely sensitive to medication adherence 23. As mentioned above, though, the use of propranolol in the face of acute intoxication is not advisable. Initial trials of modafinil also suggested that this medication may be especially beneficial for patients with more severe cocaine withdrawal symptoms who had not yet achieved a period of initial abstinence 24. In the double-blind pilot trial, modafinil was found to be useful in reducing cocaine use at a dose of up to 400 mg daily 25. Node C4. Patients with less severe cocaine withdrawal symptoms who have achieved a period of initial abstinence. Patients with less severe cocaine withdrawal symptoms and who achieved a period of initial abstinence may respond to treatment with the anticonvulsant, topiramate. In a small pilot trial, patients with less severe cocaine withdrawal symptoms as determined by low scores on the Cocaine Selective Severity Assessment (18) who had achieved at least three days of self-reported abstinence from cocaine prior to starting medications were more likely to remain abstinent at the end of a 13 week trial when treated with 200 mg daily of topiramate compared to placebo 26. Topiramate is a medication that requires a slow dose titration to avoid uncomfortable central nervous system side effects; other important side effects include paresthesias, metabolic acidosis, kidney stones, and glaucoma. In the pilot trial, topiramate was started at 25 mg daily and increased by mg weekly to a dose of 200 mg daily. Node C5. Patients with co-occurring cocaine and alcohol dependence Because disulfiram has been shown to be efficacious for the treatment of alcohol dependence, it was first used for the treatment of cocaine dependence among patients with combined cocaine and alcohol dependence. In controlled trials it has been shown to be more efficacious than placebo for the treatment of cocaine dependence in patients with co-occurring cocaine and alcohol dependence at doses up to 250 mg daily 27. The efficacy of disulfiram is not limited to patients with co-occurring alcohol dependence, however. In three other trials disulfiram was shown to be more efficacious than placebo in reducing cocaine use in cocaine-dependent patients without co-occurring alcohol dependence Indeed, a recent trial showed disulfiram to be more effective in cocaine-dependent patients without alcohol dependence than in patients with both disorders. The usefulness of disulfiram may be limited by cocaine / disulfiram interactions. Disulfiram disrupts cocaine metabolism and dopamine metabolism. Concurrent use of cocaine and disulfiram may lead to increased levels of cocaine and dopamine, potentially placing patients at increase risk for medical complications of cocaine use 31, 32. In human laboratory trials, the combination of disulfiram and cocaine resulted in increased anxiety and paranoia possibly due to increased levels of dopamine 31, 32. In clinical trials of disulfiram, serious adverse events involving cocaine disulfiram interactions have not been reported. Thus, disulfiram may be considered for the treatment of cocaine dependence in patients with and without a history of alcohol dependence. Topiramate may be effective for the treatment of patients with co-occurring alcohol and cocaine dependence. In addition to potential activity in reducing cocaine use topiramate may also be efficacious in reducing alcohol use in alcohol-dependent patients (see alcohol algorithm) 33, Although no specific trials have examined the efficacy of topiramate for patients with comorbid alcohol and cocaine dependence, clinicians may want to consider topiramate based on suggested activity for both cocaine in cocaine dependent patients and for alcohol use among alcohol dependent patients. Trials are currently underway examining the efficacy of topiramate in patients dependent upon both cocaine and alcohol. Node C6. Patients with co-occurring cocaine and opioid dependence For patients with cocaine dependence and comorbid opioid dependence, it is important to treat both substance use disorders; please consult the opioid algorithm for pharmacologic treatment approaches to opioid dependence. There is some evidence that buprenorphine, and for some patients, the combination of buprenorphine and desipramine may be page 4 of 7

5 helpful in reducing cocaine use in patients with combined opioid and cocaine dependence. First, Montoya and colleagues (2004) found that cocaine and opioid-dependent patients treated with 8 mg or 16 mg of buprenorphine every other day had less opioid and less cocaine use than did patients treated with placebo, as determined by lower levels of morphine and benzoylecgonine in urine drug screens in a 13-week trial 36. Methadone treatment is also an important option for patients with dual dependence on opioids and cocaine, as per the opioid algorithm. Kosten and colleagues (2005) found that among cocaine-dependent patients with comorbid opioid dependence, desipramine was more effective than placebo in reducing cocaine use, as measured by fewer cocaine-positive urine drug screens. This beneficial effect of desipramine was limited to patients who were maintained on bupenorphine, and was not seen in patients who were maintained on methadone. In addition, this beneficial effect of desipramine was only significant in patients who entered treatment with a urine screen that was negative for cocaine. The authors suggested that desipramine may only be efficacious among cocaine and opioid dependent patients who are maintained on buprenorphine and who have less severe cocaine dependence, or perhaps higher motivation, as determined by the ability to enter treatment with a cocaine negative urine drug screen 37. It should also be kept in mind that among cocaine dependent patients with comorbid opioid dependence maintained on methadone, desipramine and bupropion have been shown to be efficacious when combined with contingency management 8, 9. Node C7. Clinical condition improved? If successful, medications for the treatment of cocaine dependence should be expected to reduce self-reported cocaine use. It is often helpful to confirm self-reported abstinence with more objective measures of cocaine abstinence, such as urine drug screens and/or reports from family members or other third parties. Urine drug screens test for the cocaine metabolite benzoylecgonine, and generally remain positive for 1-3 days after a patient s last use of cocaine. Other measures of treatment effectiveness include instruments such as the Addiction Severity Index, which measures severity of problems in 7 domains: alcohol use, drug use, psychiatric problems, family/ social problems, medical problems, legal problems and employment problems 38. Node C8. Yes, clinical condition has improved Since most of the medications listed in this algorithm have only been evaluated in short-term, mainly preliminary, trials, little is known about the appropriate duration of treatment using these medications. Long-term efficacy has not been established for any of them. Even for medications that have achieved approval for other substance use disorders, such as alcohol dependence, the appropriate duration of treatment depends on individual circumstances. Patients who are doing well and have made the lifestyle changes necessary to support abstinence may no longer need the medication. When discontinuing any medication for the treatment of a substance use disorder, it is important to continue to closely monitor the patient for relapse. Node C9. No, clinical condition has not improved If a patient does not respond to a particular medication, a switch to another medication should be considered. The appropriate duration of a therapeutic trial would depend on the medication. Propranolol has demonstrated efficacy in an 8- week trial, as has modafinil 23, 25. Disulfiram trials have mainly been 12 weeks in duration 30. Therefore efficacy with these medications should be expected within 8-12 weeks. On the other hand, topiramate takes 6-8 weeks to titrate the dose to maximum dose and thus it may take over 10 weeks to know if topiramate will be efficacious 26. If a patient is not responding to a medication and continues to use cocaine, then clinicians should consider increasing the intensity of psychosocial support. page 5 of 7

6 References 1. Curran C, Byrappa N, McBride A. Stimulant psychosis: systematic review. British Journal of Psychiatry. 2004;185: Zimmerman JL. Poisonings and overdoses in the intensive care unit: general and specific management issues. Critical Care Medicine. 2003;31: Pitts W, Lange R, Cigarroa J, Hills L. Cocaine -induced myocardial ischemia and infarction: pathophysiology, recognition and management. Progress in Cardiovascular Diseases. 1997;40(1): Crits-Christoph P, Siqueland L, Blaine J, et al. Psychosocial treatments for cocaine dependence: National Institute on Drug Abuse Collaborative Cocaine Treatment Study. Archives of General Psychiatry. 1999;56: Rawson R, McCann M, Flammino F, et al. A comparison of contingency management, and cognitive-behavioral approaches for stimulant dependent individuals. Addiction. 2006;101: Prendergast M, Podus D, Finney J, Grenwell L, Roll J. Contingency management for treatment of substance use disorders: a metaanalysis`. Addiction. 2006;101: Weiss RD, Griffin ML, Gallop RJ, et al. The effect of 12-step self-help group attendance and participation on drug use outcomes among cocaine-dependent patients. Drug and Alcohol Dependence. 2005;77(2): Kosten T, Oliveto A, Stine S, Gonzalez G, Gonsai K. Desipramine and contingency management for cocaine and opiate dependence in buprenorphine maintained patients. Drug and Alcohol Dependence. 2003;70: Poling J, Oliveto A, Petry N, et al. Six-month trial of bupropion with contingency management for cocaine dependence in a methadone maintained population. Archives of General Psychiatry. 2006;63: MacDowell D, Nunes E, Seracini A, et al. Desipramine treatment of cocaine-dependent patients with depression: a placebocontrolled trial. Drug and Alcohol Dependence. 2005;80: Schmitz J, Averill P, Stotts A, Moeller F, Rhoades H, Grabowski J. Fluoxetine treatment of cocaine-dependent patients with major depressive disorder. Drug and Alcohol Dependence. 2001;63: Salloum I, Douaihy A, Cornelius J, Kirisci L, Kelly T, Hayes J. Divalproex utility in bipolar disorder with co-occurring cocaine dependence: a pilot study. Addictive Behaviors. 2007;32: Brown E, Perantie D, Dhanani N, Beard L, Orsulak P, Rush A. Lamotrigine for bipolar disorder and comorbid cocaine dependence: a replication and extension study. Journal of Affective Disorders. 2006;93: Smelson D, Losonczy M, Davis C, Kaune M, Williams J, Ziedonis D. Risperidone decreases craving and relapse in individuals with schizophrenia and cocaine dependence. Canadian Journal of Psychiatry. 2002;47: Beresford T, Clapp L, Martin B, Wiberg J, Alfers J, Beresford H. Aripiprazole in schizophrenia with cocaine dependence: a pilot study. Journal of Clinical Psychopharmacology. 2005;25: Sayers S, Campbell E, Kondrich J, et al. Cocaine abuse in schizophrenic patients treated with olanzapine and haloperidol. Journal of Nervous and Mental Disorders. 2005;193: Smelson D, Ziedonis D, Williams J, et al. The efficacy of olanzapine for decreasing cue-elicited craving in individuals with schizophrenia and cocaine dependence. A preliminary report. Journal of Clinical Psychopharmacology. 2006;26: Levin FR, Evans SM, Brooks DJ, Garawi F. Treatment of cocaine dependent treatment seekers with adult ADHD: Double-blind comparison of methylphenidate and placebo. Drug and Alcohol Dependence. 2007;87(1): Alterman A, McKay, JR, Mulvaney, FD, McLellan, AT. Prediction of Attrition from day hospital treatment in lower socioeconomic cocaine-dependent men. Drug and Alcohol Dependence. 1996;40: Kampman KM, Volpicelli JR, McGinnis DE, et al. Reliability and validity of the cocaine selective severity assessment. Addictive Behaviors. 1998;23(4): Kampman KM, Alterman AI, Volpicelli JR, et al. Cocaine withdrawal symptoms and initial urine toxicology results predict treatment attrition in outpatient cocaine dependence treatment. Psychology of Addictive Behaviors. 2001;15(1): page 6 of 7

7 22.Kampman KM, Volpicelli JR, Mulvaney FD, et al. Effectiveness of propranolol for cocaine dependence may depend on cocaine withdrawal symptom severity. Drug and Alcohol Dependence. 2001;63(1): Kampman K, Dackis C, Lynch K, et al. A double-blind, placebo-controlled trial of amantadine, propranolol, and their combination for the treatment of cocaine dependence in patients with severe cocaine withdrawal symptoms. Drug and Alcohol Dependence. 2006;85: Dackis C, O'Brien CP. Glutamatergic agents for cocaine dependence. Ann. N.Y. Acad. Sci. 2003;1003: Dackis C, Kampman K, Lynch K, Pettinati H, O'Brien CP. A double-blind, placebo-controlled trial of modafinil for cocaine dependence. Neuropsychopharmacology. 2005;30(1): Kampman KM, Pettinati H, Lynch K, et al. A pilot trial of topiramate for the treatment of cocaine dependence. Drug Alcohol Depend. 2004;75: Carroll K, Nich C, Ball S, McCance E, Rounsaville B. Treatment of cocaine and alcohol dependence with psychotherapy and disulfiram. Addiction. 1998;93(5): George T, Chawarski M, Pakes J, Carroll K, Kosten T, Schottenfeld R. Disulfiram versus placebo for cocaine dependence in buprenorphine-maintained subjects: a preliminary trial. Biol. Psychiatry. 2000;47(12): Petrakis I, Carroll K, Nich C, et al. Disulfiram treatment for cocaine dependence in methadone-maintained opioid addicts. addiction. 2000;95(2): Carroll K, Fenton L, Ball S, et al. Efficacy of disulfiram and cognitive behavioral therapy in cocaine dependent outpatients: a randomized placebo-controlled trial. Arch. Gen. Psychiatry. 2004;61(3): Hameedi F, Rosen M, McCance-Katz E, et al. Behavioral, physiological, and pharmacological interaction of cocaine and disulfiram in humans. Biol. Psychiatry. 1995;37(8): McCance-Katz E, Kosten T, Jatlow P. Chronic Disulfiram treatment effects on intranasal cocaine administration: initial results. Biological Psychiatry. 1998;43: Johnson BA, Ait-Daoud N, Bowden CL, et al. Oral topiramate for the treatment of alcohol dependence: a randomized controlled trial. The Lancet. 2003;361: Rubio G PG, Jimenez-Arriero MA, Palomo T, Manzanares J, Ferre F. Effects of topiramate in the treatment of alcohol dependence. Pharmacopsychiatry. 2004;37(1): Johnson BA, Rosenthal N, Capece JA, et al. Topiramate for Treating Alcohol Dependence: A Randomized Controlled Trial. JAMA. October 10, ;298(14): Montoya ID, Gorelick DA, Preston KL, et al. Randomized Trial of Buprenorphine for Treatment of Concurrent Opiate and Cocaine Dependence. Clin Pharmacol Ther. 2004;75(1): Kosten T, Sofuoglu M, Poling J, Gonsai K, Oliveto A. Desipramine Treatment for Cocaine Dependence in Buprenorphine- or Methadone-treated Patients: Baseline Urine Results as Predictor of Response. American Journal on Addictions. 2005;14(1): McLellan AT, Kushner H, Metzger D, et al. The fifth edition of the Addiction Severity Index. Journal of Substance Abuse Treatment. 1992;9: page 7 of 7