Pharmacotherapy and other treatments for cocaine abuse and dependence

PURPOSE OF REVIEW: This review examines progress being made in the treatment of cocaine abuse and dependence, with a particular focus on pharmacotherapies. Medications with apparently very different mechanisms of action have been reported to reduce cocaine use in controlled clinical trials in outpatient settings. This review will summarize the latest findings in this area. RECENT FINDINGS: Of all the medications tested to date, disulfiram has demonstrated the most consistent effect to reduce cocaine use. Several medications have been reported to reduce cocaine use in double-blind, placebo-controlled clinical trials, namely baclofen, modafinil, tiagabine, and topiramate. All pharmacotherapy trials in cocaine-dependent patients include a behavioral therapy that is common to all participants. Consequently, these pharmacotherapy trials can be considered to evaluate whether the medication is adding to the effect of the behavioral therapy. SUMMARY: Confirmatory clinical studies are necessary to replicate the initial efficacy findings for baclofen, modafinil, tiagabine, and topiramate. More research is needed in both cocaine and cocaine-alcohol dependent populations. Once confirmatory studies have been carried out, testing of rational medication combinations with different behavioral therapies is an obvious next step to increase the ability to manage cocaine dependence.     

Pharmacotherapeutic interventions for cocaine abuse. Matching patients to treatments

Cocaine abuse treatment has begun to use a variety of adjunctive pharmacotherapies. These medications have been used for both acute crash symptoms and long-term prevention of relapse. A phasic model of recovery was integrated with a patient typology to formulate guidelines for using these rapidly evolving pharmacotherapies. The phases are crash, with-drawal, and extinction, and the patient typology includes psychiatric vulnerability and severity of cocaine abuse as contributors to the neuroadaptation that requires pharmacological amelioration. These guidelines address five issues: whom to treat, when to treat, what treatments are available, where to initiate and maintain treatment, and how to match patients to treatment options.     

Seasonal cocaine abuse

The authors describe two patients with seasonal affective disorder characterized by fluctuations in cocaine craving that paralleled seasonal dysphoria. This extends the range of axis I disorders associated with cocaine self-administration.     

Pharmacologic and nonpharmacologic treatments of insomnia

Insomnia in its chronic form is present in high numbers of patients presenting to physicians. As older women who have medical problems have the highest rates of chronic insomnia, physicians must have a high index of suspicion and be prepared to explore various etiologic factors that might be operative. Treatment should focus on setting specific goals, with patients using strategies that combine lifestyle changes, behavioral interventions, and appropriate medications. OTC agents, sedating antidepressants at low dosages (trazodone, doxepin, amitriptyline, and others), and nonhypnotic benzodiazepines are insufficiently studied to provide evidence-based support for their use to treat chronic insomnia. Particularly in the elderly, close monitoring is needed to prevent falls, accidents, and cognitive impairment from these agents. FDA-labeled hypnotic agents are efficacious, but long-term studies have not been available until the recent release of eszopiclone in the United States. Recent work encourages the use of CBT even in patients who have used sleeping pills for several years, although the success of CBT has been less encouraging when applied to chronic insomnia sufferers who have concurrent psychiatric disorders and who have taken hypnotics for years.     

Nonpharmacologic treatment of cocaine abuse

This article describes nonpharmacologic techniques for treating the cocaine abuser on an outpatient basis. Key issues in assessment and treatment planning are discussed as well as specific relapse prevention strategies and success rates.     

Neurologic complications of cocaine abuse

Over a 24-month period we evaluated 14 patients with neurologic disease associated with cocaine abuse. Five patients developed previously unreported complications: anterior spinal artery syndrome, lateral medullary syndrome, transient ischemic attacks in the middle cerebral artery and vertebrobasilar artery territories, and partial motor seizures. The recent availability of crack has led to a great increase in neurologic problems associated with the use of this drug.     

The treatment of cocaine abuse

Cocaine abuse surged in the 1980s, forcing reevaluation of its previously benign image. Snorted, smoked, and injected, the drug is more widely abused than ever and, the consequences are devastating. Medical complications are frequent and range from mild (eg, cough, itching, headache) to life-threatening (eg. stroke, seizure, cardiovascular failure). Behavioral disturbances constitute the most dramatic and widespread effects of intoxication and withdrawal. Psychopathologic responses may include perceptual disturbances (eg. hallucinations) agitation, aggression, delirium, confusion, and profound delusional ideation. The goals of treatment are abstinence, rehabilitation, and relapse prevention. Hospital care may be necessary in certain circumstances. Regardless of where treatment takes place, a comprehensive program of supportive care, behavioral therapy, urine monitoring, and often psychopharmacologic intervention is required.     

Psychiatric diagnosis in cocaine abuse

The Structured Clinical Interview for DSM-III, Axis I was administered to a consecutive series of 30 cocaine abusers entering outpatient treatment. Another mental disorder was diagnosed only if its onset occurred before the onset of any substance dependence disorder. Diagnoses were made on a lifetime basis without regard to hierarchy. Most cocaine abusers had one or more additional diagnoses. We propose a model of two subtypes of cocaine abusers: (1) a primary affective disorder group, which may be split into bipolar versus unipolar or into severely versus mildly depressed subgroups; and (2) a group with other drug dependencies. The small n, limited sample, and methodological problems with diagnosis in the setting of substance abuse make these findings tentative. Future research should combine larger diagnostic studies with treatment trials to test whether such diagnostic subtypes have prognostic or treatment implications.     

Thalamomesencephalic strokes after cocaine abuse

Three young patients developed strokes of rostral midbrain and thalamus shortly following cocaine abuse. Two had infarctions and one had a hemorrhage, but none had clear risk factors other than cocaine for this relatively uncommon type of stroke. Toxicologic analysis confirmed isolated cocaine use in each patient. In the two cases of infarction studied angiographically, one had normal findings and the other had focal narrowing of the P1 segments of the posterior cerebral arteries bilaterally. Since the P1 segment has a uniquely sparse perivascular sympathetic supply, we suggest that direct adrenergic-mediated vasoconstriction is not critical to the production of cocaine-associated stroke.     

Neurovascular complications of cocaine abuse.

A 3-year prospective study of 31,081 admissions to an inner-city, emergency trauma hospital revealed 33 patients less than or equal to 45 years of age who had a total of 35 acute neurovascular events (infarction or hemorrhage) related to cocaine abuse (3% of the total 979 cocaine-related admissions). Fifty-four percent of the events were ischemic, and 46% were hemorrhagic. Six patients died. The majority (63%) of ischemic events were hemispheric and subcortical in distribution. Eleven of 13 angiograms were abnormal (five aneurysms and two arteriovenous malformations were identified). No case of "vasculitis" was seen. Seventy percent of the patients exclusively abused crack cocaine, and 94% of the neurovascular events were related to its use. No first-time cocaine users were identified. During the last year of the study, 29% of the 558 cocaine-related admissions were psychiatric admissions, and most (58%) were for treatment of depressive illness (34 patients were admitted for attempted suicide).     

Pharmacologic treatments for drug and alcohol dependence.

Pharmacotherapy remains a relatively underused strategy for the treatment of patients with psychoactive substance-use disorders. This is partly because of a widely held view among the public and the substance-abuse treatment community that substance-use disorders are non-medical and should be treated through nonpharmacologic means. Furthermore, the pharmaceutical industry has been slow in developing medications for the treatment of patients with these disorders because of skepticism over the potential profitability of such medications. These factors have limited research activity in this area, with much of the impetus for study of these medications coming from the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, where the substantial public health implications of medications development for substance-use disorders have been recognized. Despite limitations, considerable advances in medication development for patients with substance-use disorders have occurred in recent years, and more can be expected in the near future. This is most evident in the treatment of patients with nicotine and opioid dependence, for whom several pharmacologic options exist. Recently renewed interest in the pharmacologic treatment of patients with alcohol dependence is likely to advance that therapeutic area substantially with time. Ongoing efforts should focus on identifying new compounds, systematically assessing them for activity in specific substance-use disorders, and educating the public and the treatment community about the substantial benefits that can accrue from medication development for patients with substance-use disorders.     

A zolpidem and cocaine abuse case report

A case is presented of a 30-year-old man, prescribed zolpidem for insomnia arising from cocaine abuse, who sought to use this hypnotic to reduce his craving for cocaine. However, after taking cocaine and up to 300 mg/day zolpidem, he became euphoric and hyperactive. It is suggested that at high doses, zolpidem, like cocaine, has a stimulatory effect on the brain dopaminergic reward pathway. (Int J Psych Clin Pract 2002; 6: 217-219 )     

Biopsy-proven cerebral vasculitis associated with cocaine abuse

We report cerebral vasculitis in 2 cocaine users who developed symptoms (transient blindness and persistent headache) while smoking "crack," followed by progressive widespread cerebral dysfunction with focal signs over the next few weeks. One patient had smoked crack exclusively, and the other also used cocaine intravenously. Sedimentation rates were elevated and HIV titers negative. Arteriography was normal in 1 patient and in the other showed multiple large-vessel occlusions without beading. Brain biopsy showed vasculitis involving small vessels in both patients. Multinucleated cells were present in the neuropil, but there were no granulomas or evidence of infection. One patient improved significantly with corticosteroid treatment, and made a good recovery. The other died despite corticosteroid and cyclophosphamide treatment.     

Cerebral vasculitis associated with cocaine abuse.

BACKGROUND: Earlier reports of cocaine-associated cerebral vasculitis have been based primarily on angiographic findings without pathological verification. CASE DESCRIPTION: We present a case of acute encephalopathy following intravenous and intranasal administration of cocaine. Brain biopsy revealed vascular changes involving primarily small arteries. Findings included lymphocytic infiltration, endothelial thickening, and deposition of proteinaceous amorphous material within and around vessel walls. CONCLUSIONS: These abnormalities are consistent with pathological features of arteritis previously reported in association with amphetamine and multiple-drug abuse. Vasospasm-induced changes are an alternative explanation for the vascular picture seen in this case. The patient made modest improvement with high-dose intravenous steroids.     

Fluoxetine treatment of cocaine abuse in heroin addicts

The authors administered fluoxetine to 11 cocaine-abusing heroin addicts entered in a methadone maintenance program to determine whether it would decrease cocaine craving and use. Three patients discontinued treatment within a few days of initiation because of lack of any acute therapeutic effect. The remaining 8 received fluoxetine for at least 1 week and were followed up over 1 to 6 months. Of these 8, 5 (63%) were successfully treated for cocaine abuse. Three case examples are presented. Fluoxetine may prove a useful addition to the therapeutic armamentarium in the treatment of cocaine abuse.