Abstinence symptomatology and psychiatric diagnosis in cocaine abusers. Clinical observations.

Abstinence symptoms and psychiatric diagnoses were evaluated in 30 chronic cocaine abusers. Structured diagnostic interviews were done within an experimental design intended to maximize differentiation of enduring symptoms from symptoms linked to binges of cocaine use. Longitudinal evaluations showed a three-phase sequence of post-cocaine abuse abstinence symptoms. Over half the sample also met criteria for ed 3 DSM-III, axis I psychiatric disorders. The findings present specific implications for treatment design.

Comparative validity of random-interval and fixed-interval urinalysis schedules.

Accurate detection of unprescribed drug use by addicts in treatment may facilitate their rehabilitation. Many clinics collect urine samples at random, using fixed-interval collection schedules, which are not free from sampling error. Random-interval schedules minimize sampling error and consequently increase detectability of drug use by eliminating safe periods during which drug use cannot be detected. We compared these two methods by observing rates of detected opiate- and quinine-positive samples preceding and following implementation of random-interval schedules. Detected drug use doubled initially. As detection and clinical sanctions became more certain, drug use declined to well below its former level. Programs that use fixed-interval schedules may underdetect drug use by more than 50%. If patients can reliably predict safe periods, the possibility of using drugs without fear of detection may impede their rehabilitation.

Untreated opiate addicts. How do they differ from those seeking treatment?

Treatment-seeking opiate addicts were compared with an untreated, community sample identified through the chain-referral technique. Community and treatment-seeking addicts were found to be comparable in duration and severity of opiate use and in current engagement in risky, illegal activities connected with procurement of drugs. However, community addicts reported more adequate social functioning, fewer drug-related legal problems, and lower rates of depressive disorders. Despite the comparatively less severe problems in current functioning, community addicts were found to be a substantially impaired group whose failure to seek help appeared more related to misunderstanding of the severity of their drug use and of treatment opportunities than to the lack of need for help.

Cocaine abuse treatment. Open pilot trial with desipramine and lithium carbonate.

We conducted an open clinical trial of desipramine hydrochloride or lithium carbonate as adjuncts to psychotherapy in cocaine abusers. Subjects who were treated with desipramine hydrochloride showed marked decreases in a measure of cocaine craving after two to three weeks of treatment and became abstinent regardless of whether an affective disorder was also present. Lithium carbonate was effective only in cyclothymic subjects. Other subjects treated with lithium carbonate, as well as nonpharmacologically treated subjects, continued their cocaine use.

A 2.5-year follow-up of cocaine use among treated opioid addicts. Have our treatments helped?

During a 2.5-year follow-up study of opioid addicts, we found that cocaine abuse had become an increasing and major problem through 1983. Cocaine abuse had only minimally declined during the follow-up period despite treatment, and the number of opioid addicts with at least weekly cocaine abuse had doubled. The clear effect of methadone maintenance treatment in reducing opioid abuse was not evident for cocaine abuse. During the follow-up period, more cocaine use was reported by the methadone-treated subjects than by those undergoing detoxification only. Prognostically, cocaine users were more likely to be nonwhites and men. Subjects who increased their cocaine use during the follow-up period were more likely to have depressive disorders and more likely to be found among methadone- and "drug-free"-treated subjects than among detoxification subjects. Thus, among methadone- and drug-free-treated subjects, depression appeared to be a risk factor for escalating cocaine abuse; this risk factor may benefit from specific interventions.

A 2.5-year follow-up of depression, life crises, and treatment effects on abstinence among opioid addicts.

Follow-up studies have suggested that treatment increases addicts' likelihood of remaining abstinent and that depression and life crises are associated with decreased abstinence. An important issue is to what extent receiving treatment can ameliorate psychosocial risk factors such as life crises and depression and decrease ex-addicts' vulnerability to continued drug abuse. In our 2.5-year follow-up of 268 opiate addicts, drug abuse treatment was generally associated with increased abstinence, and life crises and depression were significant risk factors for continued drug abuse. The impact of these risk factors, however, was ameliorated by drug abuse treatment. Although life crises had a greater impact than depression, these two risk factors had additive effects in increasing the risk for continued drug abuse. Among the types of life crises, arguments and losses ("exits") had very strong additive effects with depression as predictors of drug abuse.

Follow-up of participants in a drug dependence therapeutic community.

We interviewed by random sample 20 graduates and 20 dropouts from a drug dependence therapeutic community to identify any differences between groups. Although the two groups were from similar backgrounds at admission, the graduates seemed to do better after treatment. Throughout the follow-up period, the graduated spent proportionately less time addicted or in jail and proportionately more time employed or in school than those who dropped out of the treatment program. At follow-up, more graduates were available for voluntary abstinence and were abstaining from addicting drugs than were the dropouts. Also, at the follow-up interview, more graduates were employed or in school and fewer were legally involved than the dropouts. In the dropout group, abstinence in the follow-up period was correlated with longer length of treatment.

Prognostic significance of psychopathology in treated opiate addicts. A 2.5-year follow-up study.

Two different methods for assessing psychopathology in opiate addicts were compared as predictors of long-term treatment outcome: (1) categorical psychiatric diagnosis using the Schedule for Affective Disorders and Schizophrenia--Lifetime Version and the Research Diagnostic Criteria and (2) global rating of psychiatric impairment using the Psychiatric Severity scale of the Addiction Severity Index (ASI). Follow-up interviews were completed 2.5 years after treatment seeking in 76% of a sample of 361 opiate addicts. Five dimensions of treatment outcome were assessed, including current functioning, psychosocial adjustment, substance use impairment, legal problems, and medical disability. Most lifetime psychiatric disorders with a prevalence of greater than 10% were significantly related to the outcome dimensions of current functioning and/or psychosocial adjustment and were unrelated to substance use impairment, legal problems, and medical disability. The ASI Psychiatric Severity rating more robustly predicted poorer functioning in the same two areas and less severe legal problems. While controlling for ASI Psychiatric Severity, the only Research Diagnostic Criteria diagnosis that remained significantly related to treatment outcome was major depression, suggesting that, as regards their prognostic characteristics, the other diagnoses are accounted for by a global underlying severity dimension.

Short-term interpersonal psychotherapy in methadone-maintained opiate addicts.

A clinical trial was used to evaluate short-term interpersonal psychotherapy (IPT) as treatment for psychiatric disorders in opiate addicts who were also participating in a full-service methadone hydrochloride maintenance program. Seventy-two opiate addicts were randomly assigned to one of two treatment conditions for six months: (1) IPT, consisting of weekly individual psychotherapy, and (2) low-contact treatment, consisting of one brief meeting per month. Recruitment was a problem, as only 5% of eligible clients agreed to participate and only around half of the subjects completed the study treatment. The outcome was similar for the two study groups. However, in many of the outcome areas, subjects in both treatment conditions attained significant clinical improvement. Several factors limited the generalizability of findings and may have biased against showing a psychotherapy effect.

Sequential patterns of multiple-drug use among high school students.

Only recently have multiple-drug use studies involving more than heroin and marijuana begun to be reported in the literature. Four of these studies have found evidence that multiple-drug use is a progressive phenomenon, although the particular pattern of multiple-drug use reported in different populations varies somewhat. This study examines the patterns of multiple-drug use reported by a random sample of 1,094 high school students living in greater New Haven, Conn in the 1972-1973 academic school year. Scalogram analysis reveals a progressive relationship for nine drugs: alcohol, marijuana, hashish, barbiturates, amphetamines, LSD, mescaline, cocaine, and heroin. Cigarettes and glue were not found to play a part in this pattern. The temporal order in which respondents reported that they had begun using each drug supports the results of scalogram analysis only in part.

The clinical use of clonidine in abrupt withdrawal from methadone. Effects on blood pressure and specific signs and symptoms.

Clonidine hydrochloride was found to be effective in the treatment of methadone hydrochloride withdrawal. Under controlled inpatient conditions established to assess dosage guidelines and to examine specific signs and symptoms of withdrawal, 20 of 25 (80%) patients were able to withdraw completely from methadone by the end of a two-week period. In most patients, ten to 11 days of clonidine administration, with a peak mean dose of 16 micro g /kg/day, resulted in a perceived reduction in symptoms compared with previous attempts to become opiate free. At these doses clonidine significantly reduced standing blood pressure without producing clinical problems. The withdrawal symptoms of anxiety, restlessness, insomnia, and muscular aching were most resistant to clonidine treatment and were reported by the majority of patients.

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.

Imipramine as treatment for depression in addicts.

This report describes the results of a placebo-controlled double-blind clinical trial evaluating imipramine hydrochloride, a tricyclic antidepressant, as treatment for depression in methadone-maintained opiate addicts. Forty-six subjects were assigned randomly to either the imipramine or placebo group for up to eight weeks. All patients also received mandatory once weekly group therapy as part of the methadone program. Outcome measures included attrition, depressive symptoms, global improvement, side effects, social functioning, and urine specimen results positive for illicit drugs. The therapeutic response in the two conditions was similar. Addicts receiving either imipramine or placebo experienced a substantial reduction of depressive symptoms during the eight weeks of the study. These findings are compared with other studies that treat depression in addicts and nonaddicts.

Clonidine and naltrexone. A safe, effective, and rapid treatment of abrupt withdrawal from methadone therapy.

Clonidine hydrochloride and naltrexone hydrochloride, given in combination, were found to provide a safe, effective, and extremely rapid treatment of abrupt withdrawal from methadone hydrochloride therapy. Under controlled inpatient conditions established to assess dosage guidelines and to examine specific signs and symptoms of withdrawal, ten (91%) of 11 patients were able to withdraw completely from methadone therapy by the end of a six-day period. Six days of clonidine hydrochloride treatment, with a peak mean dose of 2.9 mg/day on treatment day 2, attenuated the withdrawal-inducing effects of naltrexone. Naltrexone hydrochloride was gradually increased from an initial 1-mg dose on treatment day 2 to 50-mg maintenance dose on treatment day 5 without an associated increase in withdrawal symptoms. Clonidine significantly decreased BP without producing clinical problems. The withdrawal symptoms of anxiety, restlessness, and muscular aching were most resistant to treatment, but at discharge most patients were completely asymptomatic.

Clonidine in outpatient detoxification from methadone maintenance.

Inpatient narcotic detoxification with clonidine hydrochloride has been used since 1978. Outpatient withdrawal, potentially more useful, has not been adequately studied. This report describes a double-blind random assignment of 49 methadone hydrochloride-maintained patients whose dose had been lowered to 20 mg. Twenty-five were detoxified using methadone at 1-mg decrements, 24 by abrupt substitution with clonidine. Approximately 40% of both groups achieved successful detoxification, with one third maintaining abstinence over the subsequent six months. The groups were also largely equivalent on withdrawal symptoms, but the clonidine group experienced symptoms in the first half of the study and the methadone group in the second half. Clonidine appears to be a safe and efficacious outpatient treatment for opiate withdrawal, although the results were less favorable than those obtained in open or inpatient studies.

Nontolerance to the opioid antagonism of naltrexone.

Controlled opiate challenges of naltrexone-pretreated human subjects have established that naltrexone is an effective opioid antagonist. However, these challenges have been conducted after relatively acute dosing with naltrexone, and tolerance to this antagonism after chronic treatment is possible. We therefore administered morphine challenges in a double-blind, placebo-controlled design to nine ex-addicts who had been taking naltrexone for a mean of 9.4 months. None of the ex-addicts experienced euphoria; instead, most of these blockaded ex-addicts had a dysphoric histaminelike response to the intravenous morphine. The only physiological change was a slight increase in heart rate. We conclude that tolerance does not develop to the opioid antagonist properties of naltrexone up to as long as 21 months of treatment.

The combined use of clonidine and naltrexone as a rapid, safe, and effective treatment of abrupt withdrawal from methadone.

Combined clonidine and naltrexone treatment allowed 38 of 40 patients addicted to methadone to withdraw completely in 4-5 days. For most patients naltrexone was gradually increased from 1 mg/day to 50 mg/day over 4 days. Clonidine reduced the intensity of naltrexone-induced withdrawal symptoms. Clonidine significantly decreased blood pressure without producing syncope and caused sedation but no other clinical problems. The withdrawal symptoms of anxiety, anorexia, insomnia, restlessness, and muscular aching were most resistant but were mild or nonexistent at discharge. Clonidine-naltrexone treatment should succeed with patients receiving methadone doses up to 50 mg/day, facilitate naltrexone maintenance, and apply to many clinical settings.

Identifying alcoholism in treated opiate addicts.

The authors evaluated the usefulness of the Michigan Alcoholism Screening Test in detecting alcoholism (as defined by the Research Diagnostic Criteria) in opiate addicts. The test was found to be adequately sensitive and specific in detecting current cases of alcoholism but inadequate for detecting alcoholic opiate addicts whose drinking was currently under control.

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.

The treatment of narcotic withdrawal: a historical review.

The history of narcotic withdrawal treatment is filled with "cures" enthusiastically received and then quietly dropped when they turned out to be either ineffective, dangerous, or both. Methods reviewed include the Towns-Lambert belladonna treatment, sodium thiocyanate, bromide sleep treatment, Narcosan, insulin, autogenous serum, ECT, hibernation, methadone, phenothiazines, propranolol, propoxyphene, acupuncture, vitamin C, and the naloxone flush. There is need to be aware of the psychologic as well as physical aspects of withdrawal. Better detoxification techniques would help patients who are ready to discontinue the use of methadone as well as those who want to start naltrexone treatment.