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Biomedical subjects

H D Kleber

Publications and source records attributed to H D Kleber.

At least 19 recordsLinked to original sources

Dopaminergic responsivity during cocaine abstinence: a pilot study.

This preliminary study investigated dopamine (DA) function in six hospitalized cocaine-dependent subjects (DSM-III-R) who received 1.5 mg/kg of active cocaine by mouth, t.i.d., for 3 days followed by 9 days of placebo cocaine. During early and late abstinence from cocaine, plasma growth hormone (GH), homovanillic acid (HVA), prolactin, and 3-methoxy-4-hydroxyphenethyleneglycol responses to the placebo-controlled administration of oral L-dopa 250 mg/carbidopa 25 mg (Sinemet) were measured. Sinemet caused significantly greater placebo-corrected increases in GH and HVA during early as compared with late abstinence. Acute abstinence from cocaine may be associated with increased DA responsivity, which normalizes over time.

Adult

Treatment of cocaine abuse: pharmacotherapy.

Until recently the treatment of cocaine addicts was limited to non-pharmacological methods because cocaine abuse was viewed as a psychological addiction to the drug's euphoriant effects. Chronic stimulant abuse is now known to lead to neurophysiological adaptation. This physiological evidence, and the failure of many patients to respond adequately to psychological treatment, prompted clinicians and researchers to explore numerous pharmacological agents in the early 1980s. Promising medications that may affect the euphoria, the craving, withdrawal, or the toxic effects associated with cocaine are under development. Potential pharmacological agents being studied include tricyclic antidepressants, anticonvulsants, neurotransmitter precursors, stimulants and dopamine agonists, serotonin re-uptake blockers and agonists, neuroleptics and opioid agonists/antagonists. Most of the research to date is on anti-craving agents. While many positive clinical reports exist, most reports are anecdotal and uncontrolled. The available data are reviewed. Potential pharmacotherapies require further research to elucidate the differences between treatments, the target populations, the optimal dosages and duration, and the interaction with behavioural and psychotherapeutic approaches.

Cocaine

Clinical phenomenology and neurobiology of cocaine abstinence: a prospective inpatient study.

OBJECTIVE: This study was undertaken to document symptoms and changes in dopaminergic function emerging after abrupt cessation of cocaine use. METHOD: After admission, 22 patients with DSM-III-R cocaine dependence were observed drug free for 3 weeks. The patient-rated Ribicoff Abstinence Rating Scale, Symptom Rating Scale, Physical Symptom Scale, Patient Rated Anxiety Scale, Beck Depression Inventory, and visual analogue scales for 16 subjective states were completed daily, and nurses rated 13 patients with the global anxiety and depression items of the Short Clinical Rating Scale. Serial blood samples were obtained three times weekly, and the patients' levels of prolactin, growth hormone (GH), and homovanillic acid (HVA) were measured. Their prolactin and GH values were compared with those of matched normal subjects. RESULTS: A total of 62 subjective symptom variables were evaluated. At baseline, the symptom ratings were mildly elevated. At 3 weeks there were significant decreases from baseline in 28 variables and nearly significant decreases in six additional variables. Nurse-rated anxiety and depression also changed, but in a more variable pattern. There was a small but significant increase from baseline over time in plasma prolactin, but there were no significant changes in GH or HVA. The patients' prolactin and GH values did not differ from those of the normal subjects. CONCLUSIONS: These findings suggest that symptoms after inpatient cessation of uncomplicated cocaine addiction are relatively mild and decrease linearly over the first month. Evidence of dysregulated central dopamine function was limited. The findings do not support routine use of pharmacological agents in the inpatient management of such patients.

Adult

Treatment of heroin addicts using buprenorphine.

Thirty-nine opioid-dependent outpatients were treated with the partial agonist buprenorphine at 2 to 6 mg/day for 1 month. Treatment retention was good (72%), and illicit opioid use decreased from 50% overall to 17% for those who remained in treatment. Precipitated withdrawal symptoms were mild and related to dose of buprenorphine. At the end of this month, 28 subjects were abruptly discontinued from buprenorphine and given the antagonist naltrexone. Withdrawal symptoms from buprenorphine were quite mild, and naltrexone was initiated in 20 patients (51% of total or 71% of those 28 completing 30 days on buprenorphine), but only 4 patients (10% overall) were successfully maintained on naltrexone for at least 2 weeks.

Adult

The nosology of abuse and dependence.

Physicians who prescribe benzodiazepines often are asked by their patients if these drugs might be addicting or have potential for abuse. Clarifying these concepts is difficult because of numerous "gray areas" of drug use and confusion over medical criteria for such terms as "addiction", "dependence", and "tolerance". Many of the efforts to clarify the terminology regarding substance habituation, abuse, and addiction have resulted in additional confusion. They have resulted in overlapping definitions of abuse and dependence, the injection of moral judgments into scientific terms, and difficulty separating the diagnoses of the physical dependence (caused by prolonged use of a wide variety of drugs, many of which are never abused) from that of physical dependence secondary to an abusive pattern of use. This article will trace the history of the various definitions currently in use, and will suggest newer terminology to replace misleading or erroneous terms.

Anti-Anxiety Agents

Opioid antagonist challenges in buprenorphine maintained patients.

Following one month of sublingual buprenorphine treatment, 15 patients at either 2 mg (n = 7) or 3 mg (n = 8) were hospitalized and the buprenorphine was abruptly stopped by placebo substitution. On the morning following their last dose of buprenorphine, 10 patients were given 1 mg oral naltrexone and 5 were given 0.5 mg/kg intravenous naloxone in a double blind placebo controlled challenge. The naltrexone challenges produced no increase in opioid withdrawal symptoms, plasma MHPG levels, or blood pressure compared to placebo, while naloxone produced significant symptoms and blood pressure increases compared to placebo challenges.

Administration, Sublingual

Hooked on hormones? An anabolic steroid addiction hypothesis.

Widespread illicit anabolic steroid use has recently been reported. A review of available evidence suggests that elevations of serum levels of steroid hormones, including anabolic steroids, have profound psychological effects. Long-term, high-dose anabolic steroid use may lead to a preoccupation with drug use, difficulty stopping despite psychological side effects, and drug craving. Reductions in serum levels of steroid hormones appear to result in acute hyperadrenergic withdrawal symptoms that respond to steroid replacement or to agents that also ameliorate withdrawal symptoms in alcohol and opioid dependence. A delayed depression syndrome when serum steroid levels drop precipitously has been reported that appears similar to that observed in withdrawing cocaine-dependent individuals. We conclude that a proportion of anabolic steroid abusers may develop a previously unrecognized sex steroid hormone-dependence disorder and that treatment should be based on research into steroid effects on opioid and aminergic neurotransmission systems and relapse prevention.

Acute Disease

Desipramine facilitation of initial cocaine abstinence.

We conducted a double-blind, random assignment, six-week comparison of desipramine hydrochloride (n = 24), lithium carbonate (n = 24), and placebo (n = 24) treatments for cocaine dependence. Subjects were 72 outpatient cocaine abusers who met DSM-III-R dependence criteria for cocaine but not for other substance abuse. Subjects in each treatment group were similar in history of cocaine and other substance abuse, cocaine craving, sociodemographics, and other psychiatric comorbidity. Desipramine, compared with both other treatments, substantially decreased cocaine use. Lithium treatment outcome did not differ from that of placebo. Desipramine-treated subjects attained contiguous periods of abstinence substantially more frequently than subjects receiving lithium or placebo. Fifty-nine percent of the desipramine-treated subjects were abstinent for at least three to four consecutive weeks during the six-week study period, compared with 17% for placebo and 25% for lithium. Cocaine craving reductions were also substantially greater in the desipramine-treated subjects. Establishment of initial abstinence is the first stage in recovery from cocaine dependence. Our findings indicate that desipramine is an effective general treatment, for this first treatment stage, in actively cocaine-dependent outpatients.

Adult

Role of opioid antagonists in treating intravenous cocaine abuse.

Intravenous cocaine abuse is a major probel in opioid abusers including those treated in methadone maintenance. Studying 138 opioid addicts, we found that speedballing by combining opioid agonists with cocaine may be blocked by opioid antagonists such as naltrexone and by partial antagonists such as buprenorphine. With both these treatments cocaine abuse was five to eight times less than with methadone treatment.

Adult

Buprenorphine detoxification from opioid dependence: a pilot study.

Sixteen opioid dependent patients were assigned to treatment with buprenorphine for one month at three doses--2 mg (n = 10), 4 mg (n = 4), 8 mg (n = 2). Treatment retention was excellent--only one patient left due to withdrawal symptoms. Illicit opioid use was infrequent, with only 22% of the urines containing illicit opioids. Although buprenorphine dose was not associated with retention or illicit opioid use, patterns of withdrawal symptoms differed among dosage groups during the 30 day study. The 4 mg group had a substantial decline in symptoms, while the other two groups did not. Symptom levels were comparable to those during successful clonidine detoxification and much lower than those found in clonidine failures.

Adult

Differential diagnosis of psychiatric comorbidity in substance abusers.

The differential diagnosis of psychiatric comorbidity in substance abusers is important in order to provide effective pharmacological and psychotherapeutic treatments for the comorbid psychiatric disorders. Differential diagnosis of an underlying psychiatric disorder depends on the type of drug abused and the phase of abuse, ranging from acute intoxication to withdrawal. This review derives guidelines for differential diagnosis based on multiple examples of interactions between major psychiatric disorders and various abused drugs.

Acquired Immunodeficiency Syndrome