Matteo Pacini

QTc Interval Prolongation in Patients on Long-Term Methadone Maintenance Therapy

Objective: The aim of the present study was to assess the incidence of abnormal QTc interval values in a population of subjects on a long-term methadone maintenance treatment, as a single therapy, and with methadone dosages ranging between 10 and 600 mg/daily (mean ± SD = 87 ± 76). Method: Basal ECG recordings were carried out in 83 former heroin addicts on long-term successful methadone maintenance therapy for at least 6 months, while no other known QT-prolonging agent was being administered. Results: Eighty-three percent of the subjects had a more prolonged QT interval than the reference values for persons of the same sex and age. Only 2 patients displayed a QTc interval of >500 ms. No correlation emerged between QTc values and methadone dosages. Conclusion: Patients on long-term methadone maintenance treatment show longer than expected QTc interval values. This data, associated with the finding that methadone is a rather potent inhibitor of HERG potassium channels and that it may induce torsade de pointes in predisposed subjects, supports the recommendation that patients entering methadone treatment (MT) are screened for cardiac risk factors. ECG might be considered in ongoing MT patients especially before starting QT-prolonging medications.

Alcohol and cocaine use and abuse among opioid addicts engaged in a methadone maintenance treatment program.

Abstract Alcohol and cocaine abuse result in unsatisfactory treatment outcomes for heroin and illicit opioid addicts engaged in Methadone Maintenance Treatment Programs (MMTPs). This study aims to clarify the impact of MMT, which focuses on cessation of opioid abuse and diminishing psychopathology to acceptable levels (stabilization) on alcohol and cocaine abuse. Of specific interest was whether reduction of polysubstance abuse and associated psychopathological complications diminished illicit opioid abuse and/or increased retention in treatment. Changes in cocaine and alcohol use that occurred in 53 heroin addicts who had been stabilized were monitored. A control group was composed of patients terminated from treatment due to noncompliance with treatment recommendations, poor attendance, or failure to have opioid abuse stabilized, within a year. The association of psychiatric severity with alcohol and cocaine abuse in these methadone maintained patients was assessed. Cessation of illicit opioid abuse and retention in treatment are positively correlated with decrease in alcohol and cocaine abuse and the absence of the psychosocial complications associated with such abuse.

Long-Term Outcomes of Treatment-Resistant Heroin Addicts with and without DSM-IV Axis 1 Psychiatric Comorbidity (Dual Diagnosis)

Objective: The aim of this study was to compare the long-term outcomes of treatment-resistant heroin addicts with and without DSM-IV axis I psychiatric comorbidity (dual diagnosis). Method: 129 heroin addicts who also met criteria for treatment resistance, 66 with one or more DSM-IV axis I psychiatric diagnosis (DD patients), and 63 without DSM-IV axis I psychiatric comorbidity (NDD patients) were monitored prospectively (6 years on average, min. 1, max. 9) along a methadone maintenance treatment program (MMTP). Results: The rates for survival-in-treatment were about 50% for NDD patients and about 70% for DD patients. After 4 years of treatment onwards, such rates tended to become stable. DD patients showed better outcome measures than NDD patients. A significantly higher methadone dose was needed to have DD patients stabilized. Conclusions: Contrary to expectations, treatment-resistant patients with psychiatric comorbidity showed a better long-term outcome than treatment-resistant patients without psychiatric comorbidity.

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

BackgroundAddiction 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 addicts 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.MethodsUsing 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.ResultsA 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.ConclusionsThis 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.

Dual diagnosis and chronology of illness in treatment-seeking Italian patients dependent on heroin.

ABSTRACT Although there are studies describing the prevalence of patients with drug addiction and dual diagnosis, there is a paucity of data regarding the progression from psychiatric disorders to drug addiction or vice versa. A total of 1,090 patients dependent on heroin were interviewed to examine the presence of dual diagnosis and the progression from psychiatric disorders to drug dependence or vice versa. A total of 574 patients met the criteria for a dual diagnosis. A total of 362 patients progressed from substance abuse disorders to psychiatric disorders (SUD-PR) and 144 patients progressed from psychiatric disorders to drug addiction (PSY-PR). SUD-PR patients are more frequently affected by mood disorders. PSY-PR patients were more frequently diagnosed as psychotic or affected by anxiety disorders. The authors’ findings suggest that the self-medication theory of dual diagnosis was relevant only for those with existing diagnoses of schizophrenia or anxiety disorders. When treating patients with a dual diagnosis, clinicians should ensure that the same attention is given to the treatment of drug dependence as it is to the treatment of comorbid psychiatric conditions.

Differential substance abuse patterns distribute according to gender in heroin addicts.

Abstract This study attempts to analyse potential gender differences among a group of heroin addicts seeking treatment at a university-based medical centre. The central modality of treatment at this centre is the use of methadone maintenance. Among those patients entering this program there seems to be an emerging pattern of males who tend to use heroin as their opiate of choice, and are more likely to combine it with cannabis, while females are more likely to use to street methadone, with adjunctive use of ketamine, benzodiazepines, hypnotic drugs and/or amphetamines. Women are at higher risk of abusing opioids through a pathway of initial prescription painkiller use, and later to resort to street methadone to cope with prescription pain killer addiction. This latter pattern seems to result in an increased risk for fatal accidental overdoses. The use of these longer-acting agents in women may be influenced by psychosocial and hormonal factors.

Diagnostic and symptomatological features in chronic psychotic patients according to cannabis use status

Abstract The prevalence and the clinical meaning of cannabis use in patients with chronic psychosis has not been systematically explored. The authors have compared the diagnostic and symptomatological characteristics of 111 male patients affected by chronic psychosis with and without past or current use of cannabis. Sixty-six patients were still using or had used cannabis; in all cases the use preceded the onset of psychotic symptoms. Forty-three patients were cannabis-positive on urinary screening at the moment of hospitalization and 23 were currently cannabis-free but reported the use of cannabis in the past. Forty-five patients were negative on urinary screening and reported no past history of cannabis use. In evaluating the psychopathological features, the Brief Psychiatric Rating Scale (BPRS) and the Overt Aggression Rating Scale (AORS) were used. The three groups showed similar demographic data, except for age, which was lower in current cannabis users than in nonusers; no differences were found between current and past users. As regards diagnostic features, “mood cluster” was significantly better represented in cannabis users and “schizophrenic cluster” in nonusers; bipolar spectrum disorders were more frequently reported than unipolar ones. When past and current users were grouped together, only blunted affect score was significantly higher in nonusers than in users, while clastic violence showed higher scores in users. These data indicate that chronic psychosis, whether associated with past or with current use of cannabis, is frequently associated with bipolar spectrum disorders and tends to display less blunted affect and more clastic behavior.

Comparison between heroin and heroin-cocaine polyabusers: a psychopathological study.

Abstract:  The concomitant use of cocaine by heroin‐dependent subjects, or by patients on methadone maintenance treatment, is a relevant phenomenon that determines the negative consequences on health, social adjustment, and outcome of opioid addiction treatment. Little is known about the patterns of co‐use of these two substances and the pathophysiological alterations following this condition. Only a few studies have evaluated the neurochemical effects in subjects carrying this specific pattern of abuse. Similarly, the impact of cocaine abuse on psychiatric and social function in subjects already affected by opioid addiction is still poorly understood and further studies are necessary to investigate this specific area that could profoundly affect methadone maintenance treatment. The aim of this article is to investigate the psychopathological symptoms of heroin–cocaine abuse in a group of heroin addicts applying for treatment. Results show a direct relationship between cocaine abuse and a higher rate of psychiatric disorders, but a negative correlation with the severity of self‐rated psychopathology.

Is the Bipolar Spectrum the Psychopathological Substrate of Suicidality in Heroin Addicts

Background: To describe the prevalence and the risk factors of suicidal ideation in a cohort of Italian opioid addicts presenting for treatment. Method: Systematic cross-sectional clinical data on suicidal ideation, socio-demographic variables, psychiatric status, social adjustment, status and history of addiction in 616 patients were gathered. Results: Suicidal thoughts during the past week were reported by 29.1%. Suicidal thoughts were more frequent in patients with bipolar spectrum diagnoses (OR = 1.42) and in patients with depressive and aggressive symptoms (multiple R = 0.47). The odds of having suicidal thoughts were also higher for subjects receiving public welfare benefits (OR = 1.69), unemployed patients (OR = 1.37), those with early onset of heroin dependence (OR = 1.36), living alone (OR = 1.33), and experiencing problems in organizing social contacts and leisure time (OR = 1.28). Conclusion: Current suicidal ideation was a common feature of patients with opioid addiction. Depression and hostility as part of the bipolar spectrum – in the context of early-onset drug dependence, work and social/leisure problems – appear independently associated with suicidal ideation. Given the elevated rates of completed suicide in heroin addiction, these data have implications for preventing suicide in patients with this type of addiction. Prospective data are needed to further address this important clinical and public health agenda.

Clinical presentations of substance abuse in bipolar heroin addicts at time of treatment entry

BackgroundStudies on the ‘self-medication hypothesis’ have focused on substance abuse as an attempt to alleviate emotional suffering.MethodsWe have investigated concomitant substances of abuse in 150 bipolar heroin addicts clustered according to their clinical presentation at treatment entry (depressive episode, hypomanic episode, manic episode and mixed episode). Bipolar heroin addicted patients were chosen because they tend to have a concomitant poly-substance abuse and because, as compared with patients suffering for other mental illnesses, they more clearly reveal a variety of identifiable affective states.ResultsPatients with a depressive episode more frequently used non-prescribed anxiolytic-hypnotics. They were found to use cocaine-amphetamines more frequently during a hypomanic episode, whereas the use of cannabis and cocaine-amphetamines occurred more frequently during a manic episode. The associated use of alcohol, cocaine-amphetamines and cannabinoids was more frequently encountered during a mixed episode. Limitations: apart from the difficulty in determining whether the substance use modifies the mood or the mood state determines the substance used, this is a report on a retrospective analysis, rather than a study specifically designed to elucidate the issue; in addition, no information was available on the temperament of our subjects. Assessments of the same subject in various clinical presentations would have provided a better level of information.ConclusionsBesides one expected result – the prominent use of CNS stimulants during a depressive phase of bipolar patients – this study supports the hypothesis that mood elation is a pleasurable, rewarding experience that, in bipolar patients, can be started or prolonged by means of CNS stimulant drugs. Stimulant use was, therefore, more prevalent during the ‘up’ rather than the ‘down’ phase of the illness.