Abstinence Symptomatology Research Articles

Anhedonia and Reward System: Psychobiology, Evaluation, and Clinical Features

Anhedonia can be defined as a condition in which the hedonic capacity is totally or partially lost. From a psychobiological perspective, several researchers proposed that anhedonia has a putative neural substrate, the dopaminergic mesolimbic and mesocortical reward circuit, which involves the ventral tegmental area, the ventral striatum and part of the prefrontal cortex. Anhedonia is, besides depressed mood, one of the two core symptoms of depression; furthermore it is one of the most important negative symptom in schizophrenia. Anhedonia is also present in substance use disorders as part of the abstinence symptomatology, and interrelations between hedonic capability, craving and protracted withdrawal have been found, particularly in opiate-dependent subjects. Although anhedonia is regarded as an important symptom in psychopathology, so far it has received relatively little attention. In general, two main approaches have been utilized to investigate and assess anhedonia or hedonic capacity: laboratory-based measures and questionnaires. Among measurement scales, the most commonly used are the Snaith-Hamilton Pleasure Scale (SHAPS), the Fawcett-Clark Pleasure Scale (FCPS), and the Revised Chapman Physical Anhedonia Scale (CPAS). Nevertheless, other measurement scales, particularly used within broader psychopathological dimensions, are the Anhedonia-Asociality subscale (SANSanh) of the Scale for the Assessment of Negative Symptoms (SANS) and the Bech-Rafaelsen Melancholia Scale (BRMS). In this paper we analyze these different scales, individuating their strengths and limits and their current clinical applications.

Antidepressants for cocaine dependence.

Cocaine dependence is a common and serious condition, which has become nowadays a substantial public health problem. The past decade has witnessed a sustained search for an effective pharmacotherapeutic agent for the treatment of cocaine dependence. While administration of cocaine acutely increases intercellular dopamine, serotonin, and norepinephrine levels by blocking their presynaptic reuptake, chronic cocaine abuse leads to down-regulation of monoamine systems. Post-cocaine use depression and cocaine craving may be linked to this down-regulation. Antidepressant pharmacotherapy, by augmenting monoamine levels, may alleviate cocaine abstinence symptomatology, as well as relieving dysphoria and associated craving by general antidepressant action. To conduct a systematic review of all RCTs on the use of antidepressants for treating cocaine dependence. We searched the Cochrane Controlled Trials Register (Cochrane Library, issue 4, 2000), MEDLINE (from 1966 - 2000), EMBASE (from 1980 - 2000), LILACS (from 1982 - 2000), PsycLIT (from 1974 - 2000), Biological Abstracts (1982 to 2000). Other searches:reference searching; personal communication; conference abstracts; unpublished trials from pharmaceutical industry; book chapters on treatment of cocaine dependence. The inclusion criteria for all randomised controlled trials were that they should focus on the use of antidepressants on the treatment of cocaine dependence. Trials including patients with additional diagnosis such as opiate dependence were also eligible. The reviewers extracted the data independently and Relative Risks, weighted mean difference and number needed to treat were estimated. The reviewers assumed that people who died or dropped out had no improvement and tested the sensitivity of the final results to this assumption. 18 studies were included in the review, with 1177 people randomised. Positive urine sample for cocaine metabolites was the main efficacy outcome, with no significant results obtained regardless the type of antidepressant. Compared to other drugs, desipramine performed better but showing just a non significant trend with heterogeneity present as revealed by the chi-square test (8.6, df=3; p=0.04). One single trial showed imipramine performed better than placebo in terms of clinical response according to patient's self-report. A similar rate of patients remaining in treatment was found for both patients taking desipramine or placebo. Results from one single trial suggest fluoxetine patients on SSRIs are less likely to dropout. Similar results were obtained for trials where patients had additional diagnosis of opioid dependence and/or were in methadone maintenance treatment. There is no current evidence supporting the clinical use of antidepressants in the treatment of cocaine dependence. Given the high rate of dropouts in this population, clinicians may consider adding psychotherapeutic supportive measures aiming to keep patients in treatment.

Acute abstinence effects following smoked cocaine administration in humans.

Acute abstinence symptomatology following multiple deliveries of smoked cocaine was examined. Twelve crack cocaine users (male and female) participated in an inpatient study. Participants smoked 7 deliveries of cocaine on each of 4 experimental days, with each participant being exposed twice to 2 dose sizes of cocaine (0.40 vs. 0.07 mg/kg placebo). Symptoms of cocaine abstinence were measured for 6 hr following cocaine administration and again the following morning. Participants reported feeling increased craving, anxiety, and uncertainty 30 min after the 7th delivery of 0.40 mg/kg cocaine, when cocaine plasma levels were still on the descending curve. It is not clear whether these were true abstinence effects or were due to residual effects of cocaine. No significant differences were found at subsequent abstinence-assessment points. These data indicate that acute abstinence effects from smoked cocaine in a laboratory setting may be minimal.

Acute abstinence effects following smoked cocaine administration in humans.

Acute abstinence symptomatology following multiple deliveries of smoked cocaine was examined. Twelve crack cocaine users (male and female) participated in an inpatient study. Participants smoked 7 deliveries of cocaine on each of 4 experimental days, with each participant being exposed twice to 2 dose sizes of cocaine (0.40 vs. 0.07 mg/kg "placebo"). Symptoms of cocaine abstinence were measured for 6 hr following cocaine administration and again the following morning. Participants reported feeling increased craving, anxiety, and uncertainty 30 min after the 7th delivery of 0.40 mg/kg cocaine, when cocaine plasma levels were still on the descending curve. It is not clear whether these were true abstinence effects or were due to residual effects of cocaine. No significant differences were found at subsequent abstinence-assessment points. These data indicate that acute abstinence effects from smoked cocaine in a laboratory setting may be minimal.

Cocaine abstinence symptomatology and treatment attrition.

Premature termination from outpatient cocaine treatment predicts a number of poor outcomes, including higher rates of relapse and unemployment. This study attempted to predict dropouts from outpatient cocaine treatment, as well as those unable to achieve initial abstinence from cocaine, using two baseline variables that had previously been shown to predict treatment dropout: a measure of the severity of cocaine abstinence symptomatology using the Cocaine Selective Severity Assessment (CSSA) and the initial urine toxicology. Results of logistic regression analyses indicated that those with more intense abstinence symptoms, as measured by the CSSA, were five times more likely to terminate treatment prematurely. When combined with the CSSA, the initial urine did not significantly predict dropouts. The CSSA and the baseline urine were equal in their ability to predict those who would fail in their initial attempts to achieve abstinence. Implications for treatment are discussed.

Abstinence symptomatology associated with cessation of chronic cocaine abuse among methadone-maintained patients.

We assessed cocaine abstinence symptomatology in a sample of 100 cocaine-abusing, methadone-maintained patients who completed an anonymous questionnaire retrospectively rating the intensity of 18 symptoms at six time points, from 30 minutes to 2 weeks, post-cocaine use. We found that a majority of patients endorsed symptoms related to dysphoria 24 hours post-binge. However, these symptoms tended to be mild to moderate in intensity and relatively short-lived. Principal components analyses extracted four factors accounting for 64% of the variance: psychoticism, exhaustion, agitation, recovery. Early post-binge period was dominated by psychoticism and agitation, followed by recovery for the duration of the period assessed.

Stimulant withdrawal.

The current paper is a review of the literature on abstinence symptomatology after stimulant use. The studies performed indicate biological and physical changes during abstinence. One outpatient study suggests a phasic model of stimulant abstinence which is characterized by a 'crash', 'withdrawal', and 'extinction' phase. However, two inpatient studies do not confirm these findings. In contrast, these latter two studies did not find a crash phase and reported a gradual improvement of mood during these 21-day and 28-day inpatient stays. Biological measures suggest changes in receptor, endocrinological and neurochemical activity. One study found hyperprolactinemia throughout the 4-week period, while another study using PET and FDG ([18F]-Fluorodeoxyglucose) found increased brain glucose metabolism in the dopamine-rich areas of the basal ganglia and orbitofrontal cortex. Another study using PET and F18-Methylspiroperidol found decreased dopamine D2 receptor binding during cocaine withdrawal and also a separate study using PET and F-18-Dopa discovered low dopaminergic brain activity. To date, few studies have been performed, and the lack of clear-cut physical withdrawal symptoms as seen in alcohol, sedative, and opiate withdrawal makes it difficult to demonstrate definitively the presence of withdrawal during stimulant abstinence. Amphetamine withdrawal has been less studied, but empirical data suggest that the symptoms are similar to cocaine withdrawal. Further studies are needed to better delineate the presence of acute versus chronic post-use symptoms.

Cocaine dependence: alcohol and other drug dependence and withdrawal characteristics.

In this study, a cocaine abstinence syndrome is confirmed. Moreover, the cocaine withdrawal syndrome was found to be medically and psychiatrically benign and required no medication for detoxification in this inpatient setting. The 150 patients who underwent cocaine withdrawal did not show the three distinct phases of the abstinence symptomatology previously described. No patients required pharmacological intervention for cocaine withdrawal, and the dropout rate was 8% of the 150 cocaine dependents. The common symptoms of acute cessation of cocaine were transient craving, hyperactivity, slight tremor, insomnia and apprehension. The diagnosis of cocaine dependence alone without an additional drug or alcohol diagnosis was unusual in this study at 5%, as is the solitary use of cocaine also uncommon according to other studies. Studies clearly document that the concurrent and simultaneous use and dependence on multiple drugs and alcohol is present in the majority of treatment populations and common in the general population. As many as 54% of cocaine dependents qualified for alcohol dependence in this study, and many were dependent on alcohol prior to their cocaine dependence. Cocaine dependence appears to be yet another diagnosis in the spectrum of the multiple drug and alcohol dependent.

Cocaine abuse and its treatment.

Widespread use and abuse of cocaine have increased the frequency with which health professionals must manage acute and chronic intoxication and the complications stemming from drug ingestion. Acute intoxication from catecholamine excess progresses through three stages, affecting the cardiovascular, respiratory, and central nervous systems. Management is to support or return these systems to normal with sedation, beta blockade, and antiarrhythmics. Casual cocaine use is no longer considered benign, and numerous related medical complications are now recognized. Dopaminergic systems are the principal sites of reward and participate in abstinence symptomatology, putatively through depletion of dopamine and changes in receptor sensitivity and responsiveness. Long-term treatment approaches have focused on psychologic strategies of behavior modification and supportive psychotherapy. Pharmacotherapy with desipramine, amantadine, and bromocriptine was shown in preliminary studies to minimize the symptoms of cocaine withdrawal when used adjunctively with psychotherapy. The response to treatment may depend on the patient's premorbid psychiatric status.

Cocaine abuse in pregnancy: Effects on the fetus and newborn

The outcome of infants born to cocaine-using drug dependent women was compared to that of infants of non-cocaine using drug dependent and non-drug dependent women. The study population included 150 pregnant women: 50 women used heroin and methadone plus cocaine, 50 used heroin and methadone minus cocaine, and 50 were non-drug dependent women. Significant differences were found between the cocaine and drug-free groups in infant birth weight, length, head circumference and Apgar scores, with the cocaine group having lower values for each variable. Average gestational age did not vary between the 3 groups. The cocaine group included 1 spontaneous abortion and 4 fetal deaths; non-cocaine drug dependent women had 2 fetal deaths, with none in the control group. Mean abstinence scores for 19 of the physiological and behavioral parameters were lower in the cocaine group than in the non-cocaine drug dependent women with the exception of vomiting and convulsions. These data suggest that: (1) infants born to drug dependent women have a poorer general outcome than those born to non-drug dependent women; (2) maternal cocaine use does not appear to increase the incidence of severe neonatal abstinence symptomatology; (3) pregnancies complicated by cocaine abuse have a greater chance for fetal loss resulting from both spontaneous abortions and fetal death; (4) infants born to cocaine abusing women had infants with decreased birth weight, head circumference, length and Apgar scores.

COCAINE AND PREGNANCY: MATERNAL AND INFANT OUTCOME

The number of infants born to women who abuse cocaine is rapidly increasing. Subjects of this study, conducted within a drug treatment program providing pre and postnatal services to drug dependent women(DDW), included 237 pregnant women: 91 cocaine using DDW, 83 non-cocaine using DDW, and 63 non-DDW. The groups were similar for maternal age, socioeconomic status, nicotine use and parity, but differed in race. Abruptio placentae occurred in 8% of the cocaine DDW, 4% of the non-cocaine DDW and in 2% of the non-DDW. Spontaneous abortions, emergency C-sections and meconium staining occurred more often in the cocaine DDW than in either of the other 2 groups. Birth weight and length, head circumference, gestational age, and 1 min. Apgar scores were significantly lower in the infants of cocaine DDW. No differences existed in the occurrence of congenital anomalities and intracranial hemorrhage. There were more premature deliveries in the cocaine (21%) than in the non-cocaine (11%) and comparison (4%) groups. Mean neonatal abstinence scores, which incorporated 21 physiological and behavioral parameters to quantify symptoms, were lower for the cocaine exposed infants. Differences were significant with respect to cry, disturbed tremors, increased muscle tone, excoriations, fever, mottling, and loose stools. The results of this study suggest that: 1)cocaine use in pregnancy adversely effects maternal and infant outcome, 2)exposure to cocaine in-utero does not appear to increase the incidence of neonatal abstinence symptomatology.

MATERNAL DRUG USE AND THE EFFECTIVENESS OF PHARMACOTHERAPY FOR NEONATAL ABSTINENCE

Infants undergoing neonatal abstinence due to maternal drug use are commonly treated with paregoric, phenobarbital or diazepam. This study was designed to test the effectiveness of each of these agents as the first treatment drug in the control of abstinence symptomatology. The relationship of the type of maternal drug use to the effectiveness of treatment was also examined. Subjects were 134 infants treated for abstinence at Thomas Jefferson University Hospital between 1979 and 1983. Infants with serious medical complications were eliminated from the study. A series of least squares linear regression analyses was performed using the treatment drug, type of maternal drug use (opiates, non-opiates, or both), and the interaction of treatment and maternal drugs as predictors of whether or not a second pharmacotherapeutic agent was needed to bring the infant under control. Results revealed that if maternal drug use was limited to non-opiates, phenobarbital therapy was a significant predictor of successful treatment with one drug. Treating an infant with diazepam, however, significantly predicted the need for a second agent, regardless of maternal drug use. Paregoric was a significant predictor of successful treatment if maternal drug use included opiates or a combination of opiates and other drugs, and was a significant predictor of unsuccessful treatment if the mother abused only non-opiates. These results emphasize the ineffectiveness of diazepam for the treatment of neonatal abstinence as well as the relationship of maternal drug use to effective pharmacotherapy.

Heroin addiction: beta-endorphin immunoreactivity in plasma increases during withdrawal.

Seven patients with heroin addiction were hospitalized and immediately withdrawn from opiates. Abstinence symptomatology was evaluated quantitatively by use of the Himmelsbach Score. Maximal intensity of withdrawal symptomatology was reached within 2 days. beta-Endorphin immunoreactivity in plasma was measured by use of a very sensitive radioimmunoassay with a low cross-reactivity (28%) against beta-LPH. A statistically significant increase of mean plasma beta-endorphin-like immunoreactivity during withdrawal could be demonstrated.