Access to treatment with controlled medicines rationale and recommendations for neutral, precise, and respectful language.

The European Pain Federation EFIC, the International Association for Hospice and Palliative Care, International Doctors for Healthier Drug Policies, the Swiss Romandy College for Addiction Medicine, the Swiss Society of Addiction Medicine, and the World Federation for the Treatment of Opioid Dependence called on medical journals to ensure that authors always use terminology that is neutral, precise, and respectful in relation to the use of psychoactive substances. It has been shown that language can propagate stigma, and that stigma can prevent people from seeking help and influence the effectiveness of social and public-health policies. The focus of using appropriate terminology should extend to all patients who need controlled medicines, avoiding negative wording. A narrow focus on a few terms and medical communication only should be avoided. The appropriateness of terms is not absolute and indeed varies between cultures and regions and over time. For this reason, it is important that communities establish their own consensus of what is 'neutral', 'precise', and 'respectful'. We identified twenty-three problematic terms (most of them we suggest avoiding) and their possible alternatives. The use of appropriate language improves scientific quality of articles and increases chances that patients will receive the best treatment and that government policies on psychoactive substance policies will be rational.

The prevention of analgesic opioids abuse: expert opinion.

Opioids are drugs of reference for the treatment of moderate to severe pain. Their proper use and a periodic assessment of the patient are crucial to prevent misuse. A multidisciplinary group suggests strategies for all stakeholders involved in the management of pain and suggests the importance of the doctor-patient relationship.

Novel strategies to treat alcohol dependence with sodium oxybate according to clinical practice.

OBJECTIVE: The treatment of alcohol dependence (AD) with sodium oxybate (SMO) was introduced in Italy and Austria more than 20 years and 15 years ago respectively, and it is now widely employed. In addition to the data obtained from clinical trials, little information is available on specific clinical practices. Thus, the aim of this study was to present and discuss the results of a consensus meeting held after twenty years of using SMO in clinical practice in Italy. MATERIALS AND METHODS: A validated questionnaire study was conducted to investigate the modalities of treatment of AD with SMO currently used in Italy. A group of four referees first drew up the questionnaire which was distributed to fifty experts in the field of alcohol use disorders. The questionnaire consisted of 125 items with five different modalities of response and two or three answer possibilities. RESULTS: The results of this survey showed a broad consensus on some issues regarding, for example, the duration of treatment, and the dose regimen of the drug; however, some aspects of the treatment of AD with SMO still remain controversial. CONCLUSIONS: This is the first consensus study investigating the use of SMO for the treatment of AD through the opinions gained in over twenty years of clinical practice provided by fifty Italian expert clinicians. A consensus on good practice for the correct administration of SMO has clearly emerged; these opinions, along with those derived from previous clinical investigations, will help physicians to use SMO in a better way. However, some issues remain controversial, and others remain unresolved.

Substance abuse and psychosis. The strange case of opioids.

BACKGROUND: Psychoses correlated with substance abuse prove to be more common in cases involving cannabinoids, stimulants, hallucinogens, alcohol and polyabuse. Among substance abusers, it has not been ascertained whether opioids have a psychotic effect. OBJECTIVES: The aim of this review is to investigate whether, among substances of abuse, a distinction can be drawn between pro-psychotic and anti-psychotic agents on the basis of the relationship between these substances and psychosis. METHODS: Studies were identified by searching through multiple literature databases, including PubMed, Scopus, Web of Knowledge. Hand searches through reference lists of relevant reviews were used to complement the computer searches. RESULTS: Looking at the relationships linking substances of abuse with psychosis, a distinction can, in fact, be drawn between pro-psychotic and anti-psychotic substances. Even if there are no differences in the addictive processes involved, opiates are the only sedative drugs that possess an anti-psychotic effect. CONCLUSIONS: The whole topic of opiate agonism merits is due for reconsideration: it is not only the anticraving action of opiate agonism, but also its effectiveness on the psychopathological level that qualifies it as to be viewed as a powerful tool in treating mental illness.

Do Akiskal & Mallya's affective temperaments belong to the domain of pathology or to that of normality?

BACKGROUND: Kraepelin and Kretschmer hypothesized a continuum between full-blown affective pathology and premorbid temperaments. More recently Akiskal proposed a putative adaptive role for the four fundamental temperaments: the hyperthymic one characterized by emotional intensity, the cyclothymic one by emotional instability, the depressive one by a low energy level, and the irritable one by an excessive response to stimuli. Today it is widely debated whether affective temperaments belong to the domain of pathology or to that of normality. PURPOSE: To make clear, by applying an integrated model, the position of affective temperaments within the continuum between normality and pathology. METHODS: We reviewed several papers that explore the distribution of affective temperaments among the general population, and their involvement both in pathological conditions (somatic and psychiatric) and in human activities (professions and other occupations). RESULTS: Far from being intrinsically pathological conditions, affective temperaments seem to represent adaptive dispositions whose dysregulation can lead to full-blown affective pathology. All the temperamental types display some impact on people's lives by influencing personal skills and professional choices over a wide field of human activities. CONCLUSIONS: Affective temperaments are not problematic when they appear in a mild form, but when they occur in extreme form we have observed a gap between the hyperthymic temperament, which represents the most functional and desirable, and the cyclothymic, depressive, irritable and phobic anxious ones, which are closer to mood, anxiety, and substance use disorders, and imply a component of somatic diseases and life stressors.

The influence of affective temperaments and psychopathological traits on the definition of bipolar disorder subtypes: a study on bipolar I Italian national sample.

UNLABELLED: Affective temperament and psychopathological traits such as separation anxiety (SA) and interpersonal sensitivity (IPS) are supposed to impact on the clinical manifestation and on the course of Bipolar Disorder (BD); in the present study we investigated their influence on the definition of BD subtypes. METHOD: : Among 106 BD-I patients with DSM-IV depressive, manic or mixed episode included in a multi-centric Italian study and treated according to the routine clinical practice, 89 (84.0%) were in remission after a follow-up period ranging from 3 to 6 months (Clinical Global Impression-BP [CGI-BP] <2). Remitting patients underwent a comprehensive evaluation including self-report questionnaires such as the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-A) scale, Separation Anxiety Symptom Inventory (SASI), Interpersonal Sensitivity Measure (IPSM) and the Semi-structured interview for Mood Disorder (SIMD-R) administered by experienced clinicians. Correlation and factorial analyses were conducted on temperamental and psychopathological measures. Comparative analyses were conducted on different temperamental subtypes based on the TEMPS-A, SASI and IPSM profile. RESULTS: : Depressive, cyclothymic and irritable TEMPS-A score and SASI and IPSM total scores were positively and statistically correlated with each other. On the contrary, hyperthymic temperament score was negatively correlated with depressive temperament and not significantly correlated with the other temperamental and psychopathological dimensions. The factorial analysis of the TEMPS-A subscales and SASI and IPSM total scores allowed the extraction of 2 factors: the cyclothymic-sensitive (explaining 46% of the variance) that included, as positive components, depressive, cyclothymic, irritable temperaments and SASI and IPSM scores; the hyperthymic (explaining the 19% of the variance) included hyperthymic temperament as the only positive component and depressive temperament and IPSM, as negative components. Dominant cyclothymic-sensitive patients (n=49) were more frequently females and reported higher number of depressive, hypomanic and suicide attempts when compared to the dominant hyperthymic patients (n=40). On the contrary, these latter showed a higher number of manic episodes and hospitalizations than cyclothymic-sensitive patients. The rates of first-degree family history for both mood and anxiety disorders were higher in cyclothymic-sensitive than in hyperthymic patients. Cyclothymic sensitive patients also reported more axis I lifetime co-morbidities with Panic Disorder/Agoraphobia and Social Anxiety Disorder in comparison with hyperthymics. As concerns axis II co-morbidity the cyclothymic-sensitive patients met more frequently DSM-IV criteria 1, 5 and 7 for borderline personality disorder than the hyperthymics. On the contrary, antisocial personality disorder was more represented among hyperthymic than cyclothymic patients, in particular for DSM-IV criteria 1 and 6. LIMITATION: : No blind evaluation and uncertain validity of personality inventory. CONCLUSION: : Our results support the view that affective temperaments influence the clinical features of BD in terms of both clinical and course characteristics, family history and axis I and II co-morbidities. Hypothetical temperamental subtypes as measured by TEMPS-A presented important interrelationships that permit to reliably isolate two fundamental temperamental disposition: the first characterized by rapid fluctuations of mood and emotional instability, and the second by hyperactivity, high level of energy and emotional intensity. Dominant cyclothymic and hyperthymic bipolar I patients reported important differences in terms of gender distribution, number and polarity of previous episodes, hospitalizations, suicidality, rates of co-morbid anxiety and personality traits and disorders. Our data are consistent with the hypothesis that affective temperaments, and in particular cyclothymia, could be utilized as quantitative, intermediate phenotypes in order to identify BD susceptibility genes.

Supervised daily consumption, contingent take-home incentive and non-contingent take-home in methadone maintenance.

Methadone maintenance therapy (MMT) has been found effective in treating heroin addiction. Serious consideration should be given to the modality of methadone distribution, as it influences not only treatment outcome but the attitudes of policy makers and the community, too. On one hand, the choice of take-home methadone removes the need for daily attendance at a methadone clinic, which seems to improve patients' quality of life. On the other, this method, because of its lack of supervision and the absence of strict consumption monitoring, runs the risk of methadone misuse and diversion. In this study, we compared A) supervised daily consumption, B) contingent take-home incentives and C) non-contingent take-home in methadone maintenance in three groups of heroin-addicted patients attending three different MMT programmes. Retention rates at 12 months were significantly higher in contingent take-home patients (group B) than in those with supervised daily consumption (group A) and the non-contingent take-home (group C). Retention rates were higher in group A than in group C patients. Compared to patients in groups A and B, those in group C showed fewer negative urinalyses and higher rates of self-reported diversion and episodes of crime or violence. Results indicate a more positive outcomes following take-home methadone associated with behavioural incentives and other measures that aim to facilitate treatment compliance than those following daily supervised consumption. By contrast, non-contingent take-home methadone given to non-stabilized patients is associated with a high rate of diversion, along with more crime episodes and maladaptive behaviours.

Long-acting opioid-agonists in the treatment of heroin addiction: why should we call them "substitution"?

Many studies have documented the safety, efficacy, and effectiveness of long-acting opioids (L-AOs), such as methadone and buprenorphine, in the treatment of heroin addiction. This article reviews the pharmacological differences between L-AO medications and short-acting opioids (heroin) in terms of reinforcing properties, pharmacokinetics, effects on the endocrine and immune systems. Given their specific pharmacological profile, L-AOs contribute to control addictive behavior, reduce craving, and restore the balance of disrupted endocrine function. The use of the term "substitution," referring to the fact that methadone or buprenorphine replace heroin in binding to brain opioid receptors, has been generalized to consider L-AOs as simple replacement of street drugs, thus contributing to the widespread misunderstanding of this treatment approach.

The relationship of Kraepelian affective temperaments (as measured by TEMPS-I) to the tridimensional personality questionnaire (TPQ).

BACKGROUND: There is considerable uncertainty in the current literature about the relationship between personality dimensions and affective temperaments. METHOD: We compared-in a non-ill 14-26-year-old Italian student population of 1010-the affective temperaments of classic psychiatry conceived as subaffective traits [and measured through the Temperament Assessment of Memphis, Pisa, Paris and San Diego-Interview Version (TEMPS-I) in the Akiskal and Mallya Operationalization] with Cloninger's revised Tridimensional Personality Questionnaire (TPQ) deriving from the experimental psychology tradition. RESULTS: The Depressive Temperament (DT) and Harm Avoidance (HA), loaded positively on the same canonical variate, whereas the hyperthymic (HT) strongly, and Novelty Seeking (NS) moderately, loaded negatively. In contrast, the Cyclothymic Temperament (CT) loaded highly positively on a second variate, on which both Novelty Seeking strongly and Harm Avoidance moderately loaded positively. Reward Dependence (RD), Persistence (P), and Irritable Temperament (IT) did not significantly relate to any temperamental and personality constructs. At a subdimensional level of TPQ 'shyness with strangers', 'stoic rigidity', 'detachment', 'fear of uncertainty', 'reflection', and 'anticipatory worry' correlated best with the DT. 'Gregariousness', 'exploratory excitability', 'uninhibited optimism', 'attachment', 'confidence', 'extravagance', 'independence', 'vigor', and 'impulsiveness' correlated best with HT. Lastly, 'anticipatory worry', 'disorderliness', 'sentimentality', and 'fatigability' correlated best with CT. CONCLUSIONS: The data provide concurrent validity to TEMPS-I and, as earlier suggested by Cloninger, indicate that (as expected) high HA and DT are related. High NS is both related to the HT and CT, and (somewhat unexpectedly), the CT is related to high HA. In a more theoretical vein, hyperthymic-novelty seeker can be predicted to be overrepresented among those with high achievement; on the other hand, a moody, restless disposition (a cyclothymic-harm avoidant type) may engage in outrageous behavior and be liable to negative affective arousal. We submit that these considerations could shed some light on the origin of socially adaptive behavior ('sunny' or sanguine types) on the one hand, and borderline conditions, anxious-hostile bipolarity ('dark' types) on the other.

Putative clinical subtypes of social phobia: a factor-analytical study.

OBJECTIVE: To examine symptomatological subtypes of social phobia (SP) and their relationships with a number of feared situations and avoidant personality disorder (APD). METHOD: In 153 out-patients with SP according to DSM-III-R criteria, clinical subtypes were investigated by means of principal component factor analysis of the Liebowitz Social Anxiety Scale (LSAS). We compared the various SP subtypes on the basis of the highest Z-scores obtained on each LSAS factor. RESULTS: Five factors (interpersonal anxiety, formal speaking anxiety, stranger-authority anxiety, eating and drinking while being observed, anxiety of doing something while being observed) emerged, accounting for 64.7% of the total variance. When the dominant LSAS factor groups were compared, the highest values in the numbers of feared situations and the presence of APD were observed in the "interpersonal anxiety" dominant group and the lowest in the "anxiety of doing something while being observed". The "interpersonal anxiety" dominant group was the most likely to present a positive family history for SP and a lifetime comorbidity with mood disorders. CONCLUSION: The emerging multidimensional structure of phobia is congruent with, and further enriches, the existing literature.

Long-term therapy using GHB (sodium gamma hydroxybutyrate) for treatment-resistant chronic alcoholics.

Thirty-five alcohol-dependent patients according to DSM-IV criteria who also met criteria for treatment resistance were treated with doses of gamma hydroxybutyrate (GHB) ranging between 25 and 100 mg/kg/die in an open one-year study. The results show that no patients discontinued the program during the first month of treatment. Sixty percent of these patients successfully completed the protocol; 11.4% showed complete abstinence (full responder patients); 14.3% strongly reduced their alcohol intake (partial responder patients) and 34.3% of the patients were still under treatment after one year. Forty percent of the patients were nonresponders. The retention rate under treatment of the studied sample was statistically higher than that found during the last treatment of the same subjects. No significant differences were found between full responder and partial responder patients regarding changes in clinical features, alcohol intake or social adjustment. Patients still in treatment after one year significantly differed from nonresponder patients on all the variables investigated. A six-times/daily fractionated administration of the GHB dose was the only significant predictor of the retention rate.

Is mood-incongruent manic psychosis a distinct subtype?

BACKGROUND: Despite several research reports on incongruent psychotic features in mania, whether such features define a distinct disorder is unsettled. METHOD: One hundred and fifty-five inpatients with mania according to DSM-III-R were systematically evaluated in order to collect demographic and clinical information. The symptomatological evaluation was conducted by means of the Comprehensive Psychopathological Rating Scale (CPRS) and the Scale for the Assessment of Positive Symptoms (SAPS). The presence/absence of incongruent psychotic symptoms at the index episode defined two subgroups of patients, whose familial, symptomatological, clinical and course characteristics were compared. RESULTS: Eighty-six (55.5%) patients presented mood-incongruent psychotic features (MIP+). When this group was compared with the remainder of manic patients without such features (MIP-), we found substantial similarities in most demographic, familial and clinical characteristics. Despite these fundamental similarities, 4% of MIP+ vs 0% of MIP- had family history for schizophrenia (p < 0.05). We also observed a longer duration of the current episode, a higher percentage of chronic course, more suicide attempts and hospitalisations in MIP+. Moreover, other than psychotic symptoms, MIP+ showed more frequently depressive features and hostility. They also reported higher scores in social disability, especially in family and social settings. CONCLUSION: Although our findings suggest that incongruent psychotic features in the main do not distinguish two separate entities--and can be considered as hallmarks of overall severity of mania--in a small minority of cases such features appear linked to familial schizophrenia. The numerous overlapping clinical characteristics in MIP+ and MIP- raise questions about the general nosographic utility of this categorisation.

The contrasting influence of depressive and hyperthymic temperaments on psychometrically derived manic subtypes.

The present investigation focused on symptomatological subtypes of mania and their relationships with affective temperaments and other clinical features of bipolar disorder. In 153 inpatients with mania diagnosed according to DSM-III-R, symptomatological subtypes have been investigated by means of principal component factor analysis of 18 selected items of the Comprehensive Psychopathological Rating Scale (CPRS). We compared other clinical features, depressive and hyperthymic temperamental attributes, and first degree-family history for mood disorders among the various manic subtypes on the basis of the highest z-scores obtained on each CPRS factor (dominant CPRS factor groups). Five factors--Depressive, Irritable-Agitated, Euphoric-Grandiose, Accelerated-Sleepless, Paranoid-Anxious--emerged, accounting for 59.8% of the total variance. When the factor-based groups were compared, significant differences emerged in terms of the duration of the current episodes, rates of chronicity and incongruent psychotic features--being highest in the 'Depressive' and 'Paranoid-Anxious' dominant groups. The patients with highest z-scores for the 'Euphoric-Grandiose', 'Paranoid-Anxious' and 'Accelerated-Sleepless' factors were those most likely to belong to the hyperthymic temperament, while the 'Depressive' dominant group had the highest rate of depressive temperament. Finally, it is noteworthy that the 'Irritable-Agitated' group was high for both temperaments. The foregoing multidimensional structure of mania--revealing five factors--is generally concordant with the emerging literature. Consistently with our original hypothesis, a hyperthymic temperament seems to underlie the most extreme manic excitement with euphoric-accelerated-paranoid phenomenology. By contrast, the depressive temperament seemed to mute the expression of mania into a depressive-manic phenomenology.

Methadone dose and retention during treatment of heroin addicts with Axis I psychiatric comorbidity.

We studied 90 opioid-dependent subjects, 38 with one or more additional Axis I diagnosis and 52 with no psychiatric comorbidity. There were significant differences between these two groups regarding the methadone dose required for clinical stabilization, but not in the rate of retention in treatment. Dual Diagnosis patients, those with psychiatric comorbidity, required an average stabilization dose of 154 +/- 84 of methadone compared to 99 +/- 49 mg/day for patients whose only Axis I diagnosis was Opioid Dependence. In the 990-day period considered there were no differences between the two groups of patients in terms of retention in treatment.

Buprenorphine: a controlled clinical trial in the treatment of opioid dependence.

Clinical trials carried out to compare methadone and buprenorphine in the treatment of opioid dependence have generally employed an alcoholic solution of buprenorphine, which has a bioavailability superior to that of the tablets. Since the product available for large scale use is in tablet form, one intended to verify the efficacy of this formulation. In a multicentre randomised controlled double blind study, 72 opioid dependent patients were assigned to treatment with buprenorphine (8 mg/day) or methadone (60 mg/day) for a period of 6 months. The two compounds did not show any significant difference with regard to urinalyses: the average percentage of analyses proving negative was 60.4% for patients assigned to buprenorphine, and 65.5% for those assigned to methadone. With regard to retention, a non-significant trend in favour of methadone was observed. Patients completing the trial improved significantly in terms of psychosocial adjustment and global functioning, as ascertained by the DSM-IV-GAF and symptom checklist-90 (SCL-90) scales, and this was independent of the treatment group. Finally, in the case of buprenorphine, patients who dropped out differed significantly from those who stayed, in terms of a higher level of psychopathological symptoms, and a lower level of psychosocial functioning. The results of the study further support the utility of buprenorphine for the treatment of opioid dependence.

Episodic course in obsessive-compulsive disorder.

The course of obsessive-compulsive disorder (OCD) is variable, ranging from episodic to chronic. We hypothesised that the former course is more likely to be related to bipolar mood disorders. With the use of a specially constructed OCD questionnaire, we studied 135 patients fulfilling DSM-III-R criteria for OCD with an illness duration of at least 10 years and divided by course: 27.4% were episodic and 72.6% chronic. We compared clinical and familial characteristics and comorbidity. Univariate analyses showed that episodic OCD had a significantly lower rate of checking rituals and a significantly higher rate of a positive family history for mood disorder. Multivariate stepwise discriminant analysis revealed a positive and significant relationship between episodic course, family history for mood disorders, lifetime comorbidity for panic and bipolar-II disorders, late age at onset and negative correlation with generalized anxiety disorder. These data suggest that the episodic course of OCD has important clinical correlates which are related to cyclic mood disorders. This correlation has implications for treatment and research strategies on the aetiology within a subpopulation of OCD.

The semi-structured affective temperament interview (TEMPS-I). Reliability and psychometric properties in 1010 14-26-year old students.

BACKGROUND: The purpose of this study was to evaluate the reliability and psychometric properties of the Semistructured Affective Temperament Interview, and determine cut-offs for each temperament. METHOD: 1010 Italian students aged between 14 and 26 were evaluated by means of the Akiskal and Mallya criteria in a Semistructured Interview for depressive, cyclothymic, hyperthymic, and irritable temperaments. RESULTS: This instrument has very good reliability and internal consistency. The percentage of subjects with a z-score higher than the second positive standard deviation ( + 2 SD) on the scales of depressive and cyclothymic temperaments are 3.6% and 6.3% (reaching scores of 7/7 and 9/10), respectively. Hyperthymic traits, on the other hand, are widespread in our sample: most subjects are included within the second positive standard deviation ( + 2 SD), and 8.2% of these reach a 7/7 score; therefore, the problem of defining a cut-off for this temperament is still open. By contrast, the irritable temperament is rare, conforming to a non-gaussian distribution, with 2.2% of cases above the second positive standard deviation ( + 2 SD). LIMITATION: The data are based on subject report without collateral information and external validation. CONCLUSION: This study contributes to more accurate definition of cut-offs for individual temperament scales. The standardization of the interview thus makes it possible to compare three out of four temperamental scales, showing the dominant temperamental characteristics for each subject. Prospective studies are needed to demonstrate the stability of these traits over time.

TEMPS-I: delineating the most discriminant traits of the cyclothymic, depressive, hyperthymic and irritable temperaments in a nonpatient population.

BACKGROUND: Although most personality constructs have been standardized in population studies, cyclothymic, depressive, irritable and hyperthymic temperaments putatively linked to mood disorders have been classically derived from clinical observations. METHODS: We therefore administered the semi-structured affective temperament schedule of Memphis, Pisa, Paris and San Diego, Interview version (TEMPS-I) -- in its original University of Tennessee operationalization -- to 1010 Italian students aged between 14 and 26. The interview, administered in a randomized format, took 20 min per subject. RESULTS: The semi-structured interview was easy to administer and well accepted by subjects, with no refusals. Principal component analysis with varimax rotation confirmed the hypothesized four-dimensional factor structure of the interview, with good to excellent internal consistency. Furthermore, discriminant analysis and multiple regression provided suggestions for identifying the traits that are most useful in defining a weighted cut-off for each of the temperaments (and which, with minor exceptions, are in agreement with those previously proposed on clinical grounds). In an additional exploratory factorial analysis, a depressive type which loads negatively on hyperthymia was distinguished from cyclothymia; the irritable temperament did not appear to have significant loading on either factor. LIMITATION: All the present analyses were internal to the scale itself, but ongoing studies are comparing them with other systems of temperament as well as testing their clinical cogency for affectively ill populations. CONCLUSION: While more work needs to be done on better operationalization of the irritable temperament, our findings overall support the existence -- in a relatively young nonpatient population -- of cyclothymic, depressive and hyperthymic types according to the classic descriptions of Kraepelin, Kretschmer and Schneider, in their TEMPS-I operationalization. CLINICAL IMPLICATIONS: Coupled with a previous report identifying 10% of the same 14-26-year-old nonpatient population meeting an empirically defined statistical cut-off for these temperaments, the present data define the putative 'fundamental states' that Kraepelin considered to be the personal predisposing anlagé of major affective disorders.