6.5.3) TREATMENT
A) SUPPORT 1) MANAGEMENT OF MILD TO MODERATE TOXICITY a) The main therapy for cocaine withdrawal is supportive and symptomatic. Treatment goals are 3-fold: achievement of abstinence, prevention of relapse, and rehabilitation. No single treatment protocol has produced an optimal approach for all cocaine abusers. Psychiatric consulting an encouragement to participate in long-range abstinence programs are advised.
2) MANAGEMENT OF SEVERE TOXICITY a) The withdrawal syndrome following cocaine cessation is not life threatening.
3) OTHER TREATMENTS a) Dopamine agonists (pergolide), tricyclic antidepressants, and anticonvulsants have been used in the treatment of cocaine abuse and dependence, but with mixed results.
b) Cocaine Selective Severity Assessment (CSSA), a measure of 18 abstinence signs and symptoms, appears to be a reliable and valid measure of cocaine abstinence symptoms and a good predictor of negative outcomes in cocaine dependence treatment.
4) Cocaine dependency and withdrawal is a complex medical and psychosocial problem with no known effective pharmacologic therapies (Hyman, 2001; DiGregorio, 1990; Kleber & Gawin, 1984). Generally, symptoms of cocaine withdrawal are not medically dangerous and usually not seen as requiring medication intervention (Klein, 1998; Kleber, 1992). Detoxification usually requires no treatment other than abstinence and psychological counseling. Many patients find withdrawal symptoms intensely dysphoric, with drug craving. Thus, some drug therapies, described below, have been reported to benefit in relieving withdrawal and improving the prognosis, although convincing efficacy has not been demonstrated. The American Psychiatric Association in 1994 determined the DSM-IV criteria for cocaine withdrawal to include dysphoria, sleep disturbance, fatigue, increased appetite, psychomotor retardation or agitation, and unpleasant dreams. Treatment of any symptoms is symptomatic and supportive (Kampman et al, 1998; Gold, 1992). Response to pharmacologic therapy may depend on the patient's general medical status and premorbid or comorbid psychiatric status (Hyman, 2001; Hall et al, 1990). 5) Cognitive and behavioral therapies have been suggested for the prevention of relapses in patients with cocaine abuse or dependence. Some of these therapies include aversion therapy, network therapy, behavioral treatment, exposure to cocaine-related cues, contingency-based contracting, and cognitive therapy. Psychosocial support is beneficial to any therapeutic treatment regimen (Mendelson & Mello, 1996). Inconsistent results have been reported following acupuncture therapies (Lipton et al, 1994). 6) COCAINE SELECTIVE SEVERITY ASSESSMENT (CSSA), a measure of 18 abstinence signs and symptoms, appears to be a reliable and valid measure of cocaine abstinence symptoms and a good predictor of negative outcomes in cocaine dependence treatment. Initial scores appear to be higher among cocaine-dependent subjects who fail to achieve abstinence or who subsequently drop out of treatment (Mulvaney et al, 1999; Kampman et al, 1998). B) MONITORING OF PATIENT 1) No specific laboratory evaluation is needed unless otherwise indicated by the clinical status.
2) Blood or plasma cocaine concentrations are not clinically useful for guiding emergent therapy.
3) If an initial positive urine cocaine screen is found at the early stage of cocaine abstinence therapy, a 4-fold increase exists in the likelihood of failing to achieve abstinence in the first month.
4) Frequent urine laboratory testing for drugs of abuse may be indicated to screen patients for subsequent cocaine use following withdrawal.
C) DOPAMINERGIC 1) Symptoms of cocaine withdrawal or abstinence have been theorized to be the result of either dopamine depletion or dopaminergic autoreceptor supersensitivity. Thus, dopaminergic drugs have been used to relieve withdrawal symptoms and to maintain short-term abstinence (Kleber, 1995; Thompson, 1992). This approach may be potentially problematic due to effects on the cardiovascular function and temperature regulation (Klein, 1998). These agents may have some short-term anti-withdrawal effects, but effects do not persist beyond a few weeks. Dopamine agonist therapy may reduce cocaine craving, although this has not been conclusively proven in the clinical studies to date. Bromocriptine is reported as a standard treatment of acute early withdrawal symptoms, often in combination with tricyclic antidepressants (Crosby et al, 1991). a) Other agents used, but with generally disappointing or minimal results have included L-dopa, mazindol, pergolide, amantadine, lisuride, bupropion, flupentixol, tryptophan, and tyrosine. Lisuride was used in one study, with amelioration of withdrawal signs not significantly greater than that of placebo (Gillin et al, 1994).
2) BROMOCRIPTINE a) Bromocriptine, a dopamine agonist, has been advocated for therapy of cocaine withdrawal due to the "dopamine-deficit" hypothesis of cocaine dependence and the proposed reversal by bromocriptine by increasing dopaminergic tone (London et al, 1999; Johnson & Vocci, 1993; Sitland-Marken et al, 1990). In a survey of 500 physicians who treat chemical dependency, bromocriptine was the drug most often used for cocaine detoxification, and the dopamine agonists, as a class, were treatment choices for abstinence maintenance (Halikas et al, 1993). Conflicting results with bromocriptine have been reported, often with no advantage over placebo (Handelsman et al, 1997; Eiler et al, 1995). The dropout rate in bromocriptine treated patients is about 60%, mainly due to adverse effects of bromocriptine, including headaches and dizziness (Kleber, 1995). In some cases, tyrosine and tryptophan have been given concurrently with bromocriptine, theoretically, to increase concentrations of dopamine, norepinephrine, and serotonin (Sitland-Marken et al, 1990). 1) Oral doses of 0.625 mg given 4 times daily may produce a rapid decrease in psychiatric symptoms. When given in a single dose of 1.25 mg, bromocriptine has been found to decrease cocaine craving (DiGregorio, 1990). Bromocriptine dosing suggested in one study was 1.25 mg orally twice daily, with titration up to 10 mg per day within the first 7 days. Dose was decreased in patients experiencing adverse effects. This study was continued for 21 days (Eiler et al, 1995). Other studies have reported doses titrated up to 30 to 60 mg/day (Sitland-Marken et al, 1990). Clinicians should titrate doses on the basis of patients' response and side effects. Effects of bromocriptine on cocaine craving has been shown to dissipate within 3 weeks (Kleber, 1992).
3) AMANTADINE a) Amantadine, a dopamimetic agent, increases dopaminergic transmission and may have some use in the treatment of early withdrawal symptoms (eg, depression) and short-term abstinence. It is probably as effective as bromocriptine and perhaps less toxic (Huber et al, 1999; Thompson, 1992). Adverse effects to this drug may be dose-related (Crosby et al, 1991). Doses in clinical studies have included 200 mg to 400 mg orally daily for up to 12 days (Alterman et al, 1992; Barroso-Moguel et al, 1991). Effects of amantadine on cocaine craving have been shown to wear off within 3 weeks (Kleber, 1992). Further studies are needed to verify the role of amantadine in cocaine withdrawal.
4) METHYLPHENIDATE a) In the treatment of cocaine withdrawal, methylphenidate, a dopamimetic agent, has a longer duration of action and less abuse liability than cocaine. Methylphenidate may be useful in a subset of patients with residual ADHD who self-medicate with cocaine, although this is likely to be a small group. A disadvantage is a mild stimulation that can lead to a cocaine craving in persons without ADHD, who likely comprise most individuals dependent on cocaine (Crosby et al, 1991; Kleber, 1995). Dosages in the range of 20 to 30 mg per day have been given (Manschreck, 1993). Because of the potential for abuse, methylphenidate treatment should be selective and used cautiously.
5) BUSPIRONE a) Buspirone, an anxiolytic, has been used in the treatment of cocaine withdrawal due to its enhancement of dopaminergic and noradrenergic neuronal firing and suppression of serotonergic activity. Doses given in one study (10 mg 3 times/day for 30 days) were shown effective from the fifth day onward (Giannini et al, 1993). Further studies are needed to clarify the role of buspirone in cocaine withdrawal syndromes.
6) PERGOLIDE a) Pergolide has been used in the treatment of cocaine withdrawal syndrome. In one study, doses of 0.05 mg per day up to 0.15 mg 3 times daily were given, with limited success. Adverse effects included gastrointestinal complaints (Malcolm et al, 1991).
b) In a 5-year, double-blind, placebo-controlled clinical trial, 273 patients with cocaine dependence (n=273) or cocaine-alcohol dependence (n=191) were randomly assigned to receive either low-dose pergolide (n=155), high-dose pergolide (n=156), or placebo (n=153). Overall, pergolide was not effective in the treatment of cocaine dependence or in reducing alcohol use in alcohol/cocaine-dependent patients (Malcolm et al, 2000).
D) CARBAMAZEPINE 1) In animal models, carbamazepine has been shown to reverse cocaine-induced kindling and reverse dopamine receptor supersensitivity resulting from long-term cocaine use. Some open-label studies have shown that carbamazepine diminished both cocaine craving and cocaine self-administration (Halikas et al, 1993); however, placebo-controlled, double-blind studies have not shown efficacy (Kleber, 1995).
2) Doses used in an open trial of carbamazepine treatment of cocaine withdrawal included 200 to 800 mg orally 2 to 4 times daily (Mendelson & Mello, 1996; Halikas et al, 1993).
3) ANTICONVULSANTS: In a review article of 15 studies (n=1066), the use of carbamazepine, gabapentin, lamotrigine, phenytoin, tiagabine, topiramate, or valproate were not significantly effective in treating patients with cocaine dependence as compared with placebo. In 2 studies (n=81), placebo was superior to gabapentin in reducing the number of dropouts (Relative Risk [RR] 3.56 [95% Confidence Interval [CI] 1.07 to 11.82]). In 2 studies (n=56), more adverse effects developed in patients receiving phenytoin compared with placebo (Relative Risk [RR] 2.12 [95% Confidence Interval [CI] 1.08 to 4.17]). In addition, more adverse effects developed in patients (n=95) receiving gabapentin in one study as compared with placebo (Minozzi et al, 2008).
E) BUPRENORPHINE 1) Buprenorphine, an opioid mixed agonist/antagonist, has been used in the treatment of persons with concurrent cocaine and opioid dependence. This drug may decrease the enhanced high of heroin and cocaine taken together ("speed-ball") (Kleber, 1995). Clinical trials have suggested that buprenorphine reduces cocaine abuse as well as opiate abuse (Mendelson & Mello, 1996).
F) PSYCHOMOTOR AGITATION 1) INDICATION a) If patient is severely agitated, sedate with IV benzodiazepines.
2) DIAZEPAM DOSE a) ADULT: 5 to 10 mg IV initially, repeat every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
3) LORAZEPAM DOSE a) ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed (Manno, 2003).
b) CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
4) Extremely large doses of benzodiazepines may be required in patients with severe intoxication in order to obtain adequate sedation. Titrate dose to clinical response and monitor for hypotension, CNS and respiratory depression, and the need for endotracheal intubation. 5) Buprenorphine, an opioid mixed agonist/antagonist, has been used in the treatment of persons with concurrent cocaine and opioid dependence. This drug may decrease the enhanced high of heroin and cocaine taken together ("speed-ball") (Kleber, 1995). Clinical trials have suggested that buprenorphine reduces cocaine abuse as well as opiate abuse (Mendelson & Mello, 1996). G) DEPRESSIVE DISORDER 1) Depressive symptoms during the acute post-cocaine phase are usually transient and require no treatment other than close observation. It has been hypothesized that tricyclic antidepressants may reduce dopaminergic receptor sensitivity and thus may reverse cocaine-induced dopaminergic supersensitivity (Johnson & Vocci, 1993; Crosby et al, 1991). 2) Desipramine has been used with equivocal results; it appears to be of most benefit in patients who have antecedent or consequent symptoms of severe depression. Trazodone and imipramine have also been tried but had more adverse effects than desipramine (Mendelson & Mello, 1996). a) Tricyclic antidepressants may be useful for selected cocaine users with comorbid depression or intranasal use (Nunes et al, 1995). Tricyclic antidepressants (specifically desipramine, imipramine, and maprotiline), bupropion, lithium, and methylphenidate have been used to treat cocaine withdrawal with mixed success (Kleber & Gawin, 1984). b) DESIPRAMINE, with a slow onset of action, is sometimes added to a bromocriptine regimen, a drug with a rapid onset of action, to enhance therapeutic effects. Desipramine has been shown to facilitate abstinence at dosages of approximately 200 mg per day (Manschreck, 1993; Kleber, 1992; Crosby et al, 1991). 1) In a double-blind, randomized, 6-week comparison study of desipramine (n=24), lithium carbonate (n=24), and placebo (n=24) for cocaine dependence, despiramine-treated patients were more frequently abstinent, were abstinent for longer periods, and had less craving for cocaine. Overall, cocaine abstinence for at least 3 to 4 consecutive weeks was observed in 59% of despiramine-treated patients compared with 25% of patients in the lithium group and 17% of patients in the placebo group (Gawin et al, 1989).
c) IMIPRAMINE has been used for treatment of selected cocaine abusers with comorbid depression in doses up to 300 mg/day (Nunes et al, 1995). d) TRAZODONE has been used for treatment of crack-cocaine-induced compulsive behavior. It was speculated that trazodone reduced craving due to trazodone's serotonin reuptake inhibitory action (Khouzam et al, 1995). Doses of 150 mg up to 200 mg daily have been used. e) LITHIUM CARBONATE may facilitate abstinence and attenuate the euphoric reaction to cocaine, although human studies to date have not achieved good results. It appears to be most effective in a subset of patients with a concurrent diagnosis of bipolar disorder (Manschreck, 1993; Kleber, 1992). Doses have been given to sustain lithium blood levels at 0.6 to 1.1 mEq/L (Hall et al, 1990). 1) In a double-blind, randomized, 6-week comparison study of desipramine (n=24), lithium carbonate (n=24), and placebo (n=24) for cocaine dependence, despiramine-treated patients were more frequently abstinent, were abstinent for longer periods, and had less craving for cocaine. Overall, cocaine abstinence for at least 3 to 4 consecutive weeks was observed in 59% of despiramine-treated patients compared with 25% of patients in the lithium group and 17% of patients in the placebo group (Gawin et al, 1989).
H) PSYCHOTIC DISORDER 1) Antipsychotics such as chlorpromazine, haloperidol, and promazine have been used successfully to manage patients with psychotic symptoms associated with cocaine dependence and withdrawal. Typically, cocaine psychosis lasts about 3 to 5 days following cessation of cocaine use. If psychosis lasts longer, or if the patient becomes increasingly difficult to manage, an antipsychotic medication may be tried. Phenothiazine derivatives have been tried in the control of impulsive behavior and to decrease cocaine craving, although adverse effects may limit their acceptability (Crosby et al, 1991; Kleber & Gawin, 1984).
|