Subtyping patients with heroin addiction at treatment entry: factor derived from the Self-Report Symptom Inventory (SCL-90)

<p>Abstract</p> <p>Background</p> <p>Addiction is a relapsing chronic condition in which psychiatric phenomena play a crucial role. Psychopathological symptoms in patients with heroin addiction are generally considered to be part of the drug addict's personality, or else to be related to the presence of psychiatric comorbidity, raising doubts about whether patients with long-term abuse of opioids actually possess specific psychopathological dimensions.</p> <p>Methods</p> <p>Using the Self-Report Symptom Inventory (SCL-90), we studied the psychopathological dimensions of 1,055 patients with heroin addiction (884 males and 171 females) aged between 16 and 59 years at the beginning of treatment, and their relationship to age, sex and duration of dependence.</p> <p>Results</p> <p>A total of 150 (14.2%) patients with heroin addiction showed depressive symptomatology characterised by feelings of worthlessness and being trapped or caught; 257 (24.4%) had somatisation symptoms, 205 (19.4%) interpersonal sensitivity and psychotic symptoms, 235 (22.3%) panic symptomatology, 208 (19.7%) violence and self-aggression. These dimensions were not correlated with sex or duration of dependence. Younger patients with heroin addiction were characterised by higher scores for violence-suicide, sensitivity and panic anxiety symptomatology. Older patients with heroin addiction showed higher scores for somatisation and worthlessness-being trapped symptomatology.</p> <p>Conclusions</p> <p>This study supports the hypothesis that mood, anxiety and impulse-control dysregulation are the core of the clinical phenomenology of addiction and should be incorporated into its nosology.</p

Antidepressants for the treatment of people with co-occurring depression and alcohol dependence

Background Alcohol dependence is a major public health problem characterized by recidivism, and medical and psychosocial complications. The co-occurrence of major depression in people entering treatment for alcohol dependence is common, and represents a risk factor for morbidity and mortality, which negatively influences treatment outcomes. Objectives To assess the benefits and risks of antidepressants for the treatment of people with co-occurring depression and alcohol Search methods We searched the Cochrane Drugs and Alcohol Group Specialised Register (via CRSLive), Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from inception to July 2017. We also searched for ongoing and unpublished studies via ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (apps.who.int/trialsearch/). All searches included non-English language literature. We handsearched references of topic-related systematic reviews and the included studies. Selection criteria Randomized controlled trials and controlled clinical trials comparing antidepressants alone or in association with other drugs Antidepressants for the treatment of people with co-occurring depression and alcohol dependence or psychosocial interventions (or both) versus placebo, no treatment, and other pharmacological or psychosocial interventions. Data collection and analysis We used standard methodological procedures as expected by Cochrane. Main results We included 33 studies in the review (2242 participants). Antidepressants were compared to placebo (22 studies), psychotherapy (two studies), other medications (four studies), or other antidepressants (five studies). The mean duration of the trials was 9.9 weeks (range 3 to 26 weeks). Eighteen studies took place in the USA, 12 in Europe, two in Turkey, and one in Australia. The antidepressant included in most of the trials was sertraline; other medications were amitriptyline, citalopram, desipramine, doxepin, escitalopram, fluoxetine, fluvoxamine, imipramine, mianserin, mirtazepine, nefazodone, paroxetine, tianeptine, venlafaxine, and viloxazine. Eighteen studies were conducted in an outpatient setting, nine in an inpatient setting, and six in both settings. Psychosocial treatment was provided in 18 studies. There was high heterogeneity in the selection of outcomes and the rating systems used for diagnosis and outcome assessment. Comparing antidepressants to placebo, low-quality evidence suggested that antidepressants reduced the severity of depression evaluated with interviewer-rated scales at the end of trial (14 studies, 1074 participants, standardized mean difference (SMD) -0.27, 95% confidence interval (CI) -0.49 to -0.04). However, the difference became non-significant after the exclusion of studies with a high risk of bias (SMD -0.17, 95% CI -0.39 to 0.04). In addition, very low-quality evidence supported the efficacy of antidepressants in increasing the response to the treatment (10 studies, 805 participants, risk ratio (RR) 1.40, 95% Cl 1.08 to 1.82). This result became non-significant after the exclusion of studies at high risk of bias (RR 1.27, 95% CI 0.96 to 1.68). There was no difference for other relevant outcomes such as the difference between baseline and final score, evaluated using interviewer-rated scales (5 studies, 447 participants, SMD 0.15, 95% CI -0.12 to 0.42). Moderate-quality evidence found that antidepressants increased the number of participants abstinent from alcohol during the trial (7 studies, 424 participants, RR 1.71, 95% Cl 1.22 to 2.39) and reduced the number of drinks per drinking days (7 studies, 451 participants, mean difference (MD) -1.13 drinks per drinking days, 95% Cl -1.79 to -0.46). After the exclusion of studies with high risk of bias, the number of abstinent remained higher (RR 1.69, 95% CI 1.18 to 2.43) and the number of drinks per drinking days lower (MD -1.21 number of drinks per drinking days, 95% CI -1.91 to -0.51) among participants who received antidepressants compared to those who received placebo. However, other outcomes such as the rate of abstinent days did not differ between antidepressants and placebo (9 studies, 821 participants, MD 1.34, 95% Cl -1.66 to 4.34; low quality evidence). Low-quality evidence suggested no differences between antidepressants and placebo in the number of dropouts (17 studies, 1159 participants, RR 0.98, 95% Cl 0.79 to 1.22) and adverse events as withdrawal for medical reasons (10 studies, 947 participants, RR 1.15, 95% Cl 0.65 to 2.04). There were few studies comparing one antidepressant versus another antidepressant or antidepressants versus other interventions, and these had a small sample size and were heterogeneous in terms of the types of interventions that were compared, yielding results that were not informative. Authors' conclusions We found low-quality evidence supporting the clinical use of antidepressants in the treatment of people with co-occurring depression and alcohol dependence. Antidepressants had positive effects on certain relevant outcomes related to depression and alcohol use but not on other relevant outcomes. Moreover, most of these positive effects were no longer significant when studies with high risk of bias were excluded. Results were limited by the large number of studies showing high or unclear risk of bias and the low number of studies comparing one antidepressant to another or antidepressants to other medication. In people with co-occurring depression and alcohol dependence, the risk of developing adverse effects appeared to be minimal, especially for the newer classes of antidepressants (such as selective serotonin reuptake inhibitors). According to these results, in people with co-occurring depression and alcohol dependence, antidepressants may be useful for the treatment of depression, alcohol dependence, or both, although the clinical relevance may be modest

Antidepressants for the treatment of people with co-occurring depression and alcohol dependence.

We found low-quality evidence supporting the clinical use of antidepressants in the treatment of people with co-occurring depression and alcohol dependence. Antidepressants had positive effects on certain relevant outcomes related to depression and alcohol use but not on other relevant outcomes. Moreover, most of these positive effects were no longer significant when studies with high risk of bias were excluded. Results were limited by the large number of studies showing high or unclear risk of bias and the low number of studies comparing one antidepressant to another or antidepressants to other medication. In people with co-occurring depression and alcohol dependence, the risk of developing adverse effects appeared to be minimal, especially for the newer classes of antidepressants (such as selective serotonin reuptake inhibitors). According to these results, in people with co-occurring depression and alcohol dependence, antidepressants may be useful for the treatment of depression, alcohol dependence, or both, although the clinical relevance may be modest

QTc interval screening for cardiac risk in methadone treatment of opioid dependence.

No evidence has been found to support the use of the electrocardiogram (ECG) for preventing cardiac arrhythmias in methadone-treated opioid dependents. A maintenance program with methadone is an effective treatment for people who are dependent on opioids, in terms of increased retention in treatment, reduced use of opioids, reduced human immunodeficiency virus (HIV) transmission and reduced mortality. Nowadays methadone represents the most frequently used medication for this disorder. However, the use of methadone has been associated with a potentially fatal cardiac arrhythmia called torsade de pointes (TdP). Evidence supporting the relationship between methadone and TdP is limited. However, given the risk involved for the life of patients, consensus and recommendations for patients receiving methadone treatment have been developed. Recommended procedures aim to identify patients who present a specific alteration of the ECG, represented by prolongation of the QT interval, which is considered a marker for arrhythmias such as TdP. Patients identified as at risk may then be provided with alternative treatment (reduction of methadone dosage; provision of alternative opioid agonist treatment; treatment of associated risk factors). However, the acceptability of ECG screening has been questioned because the procedures involved may be too demanding and stressful, may interfere with the availability of patients to undergo methadone maintenance and may expose patients to health consequences of untreated opioid addiction, including increased mortality risk. This review looked at the evidence on the efficacy and acceptability of such ECG-based screening procedures. Even though the search was extended to different experimental and non- experimental study designs, the authors did not find any study that fulfilled methodological criteria for the review. Therefore, it is not possible to draw any conclusions about the effectiveness of ECG-based screening strategies for preventing cardiac morbidity/mortality in methadone-treated opioid addicts. Research efforts should focus on strengthening the evidence about the effectiveness of widespread implementation of such strategies and clarifying associated benefits and harms

Antidepressants for cocaine dependence and problematic cocaine use.

A pharmacological agent with proven efficacy does not exist for treatment of cocaine dependence. Cocaine is an alkaloid derived from the erythroxylon coca leaf that is used as powder for intranasal or intravenous use or as crack, a free-base form which is smoked. Cocaine dependence is a major public health problem because its use can be associated with medical and psychosocial complications including the spread of infectious diseases (such as AIDS, hepatitis and tuberculosis), crime, violence and neonatal drug exposure. This review looked at the evidence on the efficacy and acceptability of antidepressants alone or in combination with a psychosocial intervention for the treatment of cocaine abuse and dependence. Current evidence from randomised controlled trials does not support the use of antidepressants. Positive results obtained by antidepressants on mood-related outcomes are consistent with the primary effect of antidepressants. They do not seem to be associated with any effect on dropouts from treatment, cocaine use or side effects, which are direct indicators of cocaine abuse and dependence. A total of 37 randomised controlled clinical studies involving 3551 participants were included in the review. All the studies except one took place in the USA; 33 trials were conducted with outpatients in the community or in mental health centres. In 10 trials patients were also treated for opioid dependence with methadone or buprenorphine. The antidepressants included desipramine, fluoxetine and bupropion and the mean duration of the trials was 10.7 weeks. The included studies utilised 43 different rating instruments and differed in design, quality, characteristics of patients, tested medication, services and the treatments delivered

Anticonvulsants for alcohol dependence.

Background: Alcohol dependence is a major public health problem characterised by recidivism and a host of medical and psychosocial complications. Together with psychosocial interventions, different pharmacological interventions have been tested in trials and systematic reviews. In this review, we wanted to discover whether anticonvulsants are better than placebo or are better than other medications, psychosocial interventions or no intervention. Authors' conclusions: At the current stage of research, evidence supporting the clinical use of anticonvulsants to treat alcohol dependence is insufficient. Results are conditioned by heterogeneity and by the low number and quality of studies comparing anticonvulsants versus other medications. The uncertainty associated with these results leaves to clinicians the need to balance the possible benefits/risks of treatment with anticonvulsants versus other medications as supported by evidence of efficacy

Pharmacological treatment for depression during opioid agonist treatment for opioid dependence.

Objectives: To evaluate the efficacy and the acceptability of antidepressants for the treatment of depressed opioid dependents treated with opioid agonists. There is little evidence to support the use of antidepressants for treating people who are dependent on opioids and have clinical depression. Depression is more common in people with substance abuse and dependence than in the general population. The depression experienced is also associated with an increased risk of completed suicide. Depression may represent an independent disorder, the psychosocial stress associated with addictive behavior or it could be a consequence of drug use and drug withdrawal effects. A maintenance program with opioid agonists (methadone, buprenorphine, LAAM) is an effective treatment for people who are dependent on opioids in terms of retention in treatment and reduced use of opioids. Depression is however still prevalent and negatively impacts on treatment outcomes. Treatment with antidepressant drugs has therefore been proposed. These adjunct drug treatments include tricyclic antidepressants (doxepin, desipramine, imipramine) and selective serotonin reuptake inhibitors (SSRIs fluoxetine, sertraline). Authors included seven randomised controlled studies that involved 482 participants in our review. The studies were conducted in outpatient settings over four to 16 weeks; six were in USA and one in Australia. The mean age of participants was 34 years and 62% were males. No clear difference was found in the number of dropouts from an opioid agonist maintenance program between people receiving antidepressants and those in the placebo groups. Neither was drug use different (two studies). Severity of depression was reduced with the use of antidepressants (two studies), including tricyclic antidepressants. Adverse events were important as more of the participants who received antidepressants withdrew from the studies for medical reasons compared with those participants on placebo (four studies). The differences between studies in clinical (participant characteristics, the medications used, services and treatments delivered) and methodological characteristics (study design and quality) made it difficult to draw confident conclusions about the efficacy and safety of antidepressants for the treatment of depression in people who are dependent on opioids

Disulfiram for the treatment of cocaine dependence.

Objective: To evaluate the efficacy and the acceptability of disulfiram for cocaine dependence. Cocaine is used as powder for intranasal or intravenous use, or smoked as crack. Dependence on cocaine can cause major public health problems because of its psychological, social and medical impacts, including the spread of infectious diseases such as AIDS, hepatitis and tuberculosis. No proven pharmacological treatment of cocaine dependency exists as yet. Disulfiram is marketed for the treatment of alcoholism and interferes with the metabolism of alcohol. It may also be useful in treating cocaine dependence. Evidence from randomised controlled trials to support the clinical use of disulfiram in people with cocaine dependence is limited. The review authors identified seven controlled studies that randomised a total of 492 participants to receive disulfiram, a placebo, no pharmacological treatment or naltrexone in addition to psychosocial treatment. Their mean age was 38 years and the studies took place in an outpatient setting over a mean time of 12 weeks. All trials but one were conducted in the USA. Five studies enrolled patients with cocaine dependence and alcohol abuse or dependence. Two enrolled people with concurrent opioid addiction who were undergoing treatment with buprenorphine or methadone. Disulfiram showed a trend toward fewer dropouts from psychosocial treatment when compared to placebo (three trials) or naltrexone (three trials) but this was not statistically significant. Assessing cocaine use, single studies were in favour of disulfiram on number of weeks of abstinence in one out of four comparisons when compared with placebo and on maximum weeks of consecutive abstinence and number of people achieving three or more weeks of consecutive abstinence in one study comparing disulfiram to no pharmacological treatment. The included studies did not specifically investigate the adverse effects of disulfiram itself or its potential to increase alcohol and cocaine adverse effects

Delineating the Psychic Structure of Substance Use and Addictions, from Neurobiology to Clinical Implications: Ten Years Later

The diagnosis of substance use disorder is currently based on the presence of specifically identified behavioral symptoms. In addition, other psychiatric signs and symptoms accompany addictive behavior, contributing to the full picture of patients’ psychopathologic profile. Historically, such symptoms were confined within the framework of “comorbidity”, as comorbid psychiatric disorders or personality traits. However, an alternative unitary view of the psychopathology of addiction, inclusive of related psychiatric symptoms, has been claimed, with the support of epidemiological, neurobiological, and neuropsychological evidence. In the present article, we highlight the research advancements that strengthen this unified perspective. We then give an account of our group’s definition of a specific SCL-90-based construct of the psychopathology of addiction. Lastly, we discuss the benefits that can be expected to be acquired in the evaluation and treatment of patients with a longitudinal approach including psychological/psychiatric predisposing features, addictive behavior, and psychiatric manifestations

Disulfiram for the treatment of cocaine dependence

Background: Cocaine is a psychostimulant used by approximately 0.4% of the general population worldwide. Cocaine dependence is a chronic mental disorder characterised by the inability to control cocaine use and a host of severe medical and psychosocial complications. There is current no approved pharmacological treatment for cocaine dependence. Some researchers have proposed disulfiram, a medication approved to treat alcohol use disorder. This is an update of a Cochrane review first published in 2010. Objectives: To evaluate the efficacy and safety of disulfiram for the treatment of cocaine dependence. Search methods: We updated our searches of the following databases to August 2022: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and PsycINFO. We also searched for ongoing and unpublished studies via two trials registries. We handsearched the references of topic-related systematic reviews and included studies. The searches had no language restrictions. Selection criteria: We included randomised controlled trials that evaluated disulfiram alone or associated with psychosocial interventions versus placebo, no intervention, other pharmacological interventions, or any psychosocial intervention for the treatment of cocaine dependence. Data collection and analysis: We used standard methodological procedures expected by Cochrane. Main results: Thirteen studies (1191 participants) met our inclusion criteria. Disulfiram versus placebo or no treatment Disulfiram compared to placebo may increase the number of people who are abstinent at the end of treatment (point abstinence; risk ratio (RR) 1.58, 95% confidence interval (CI) 1.05 to 2.36; 3 datasets, 142 participants; low-certainty evidence). However, compared to placebo or no pharmacological treatment, disulfiram may have little or no effect on frequency of cocaine use (standardised mean difference (SMD) -0.11 standard deviations (SDs), 95% CI -0.39 to 0.17; 13 datasets, 818 participants), amount of cocaine use (SMD -0.00 SDs, 95% CI -0.30 to 0.30; 7 datasets, 376 participants), continuous abstinence (RR 1.23, 95% CI 0.80 to 1.91; 6 datasets, 386 participants), and dropout for any reason (RR 1.20, 95% CI 0.92 to 1.55; 14 datasets, 841 participants). The certainty of the evidence was low for all these outcomes. We are unsure about the effects of disulfiram versus placebo on dropout due to adverse events (RR 12.97, 95% CI 0.77 to 218.37; 1 study, 67 participants) and on the occurrence of adverse events (RR 3.00, 95% CI 0.35 to 25.98), because the certainty of the evidence was very low for these outcomes. Disulfiram versus naltrexone Disulfiram compared with naltrexone may reduce the frequency of cocaine use (mean difference (MD) -1.90 days, 95% CI -3.37 to -0.43; 2 datasets, 123 participants; low-certainty evidence) and may have little or no effect on amount of cocaine use (SMD 0.12 SDs, 95% CI -0.27 to 0.51, 2 datasets, 123 participants; low-certainty evidence). We are unsure about the effect of disulfiram versus naltrexone on dropout for any reason (RR 0.86, 95% CI 0.56 to 1.32, 3 datasets, 131 participants) and dropout due to adverse events (RR 0.50, 95% CI 0.07 to 3.55; 1 dataset, 8 participants), because the certainty of the evidence was very low for these outcomes. Authors' conclusions: Our results show that disulfiram compared to placebo may increase point abstinence. However, disulfiram compared to placebo or no pharmacological treatment may have little or no effect on frequency of cocaine use, amount of cocaine use, continued abstinence, and dropout for any reason. We are unsure if disulfiram has any adverse effects in this population. Caution is required when transferring our results to clinical practice