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.

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.

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.

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.

Interaction between the serotonin and dopamine systems in humans: preliminary findings.

The availability of peripheral tools, such as platelet [3H]-imipramine binding and electroretinogram b-wave amplitude, for investigating serotonin and dopamine systems respectively, prompted us to explore the possible relationships between these two systems in a group of 8 healthy drug-free volunteers. The results showed a significant correlation between the peripheral parameters of serotonin and dopamine systems and underline the importance of studying different neurotransmitters at the same time in humans.

Methadone dosages and therapeutic compliance during a methadone maintenance program.

In 97 heroin addicts in a methadone maintenance treatment program (MMTP) with social services, urine screening for opioid metabolites identified groups with different treatment compliance. The positive correlation between compliance and methadone dosage confirms that MMTPs are effective in rehabilitating patients when 'adequate' dosage, i.e., capable of preventing relapse, is used.

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.

Effects of phototherapy on non-seasonal unipolar and bipolar depressive spectrum disorders.

In a group of 17 patients with non-SAD depressive disorders we compared the response of bipolar spectrum versus unipolar patients to treatment with light therapy. The main hypothesis was that bipolar spectrum depressed patients would preferentially respond to bright light therapy as compared to unipolar depressed patients. All patients were treated with either 400 or 2500 lux phototherapy for 2 h on seven consecutive days. All outcome measures, which included the SIGH-SAD, CGI, and the Anxiety and Depressive Factors of the SCL-90, showed significant improvement in the bipolar vs. the unipolar spectrum patients. Unexpected this occurred regardless of the intensity of the light. These changes were judged to be quite clinically significant. All patients showing response were noted to have maintained their response at a 3-month follow-up.

Impairment of work and leisure in depressed outpatients. A preliminary communication.

In a detailed analysis of the effects of depression on a broad range of social, marital, vocational adjustment and leisure time activities in 176 outpatients with mild to moderate depressions, major disturbances were seen in all areas of functioning. These disturbances were most pronounced in the areas of work and social leisure. Except for continued impairment in leisure, these disturbances were considerably attenuated in those patients who were at a mild or asymptomatic level of depression at the time of comparison. These data suggest that functions which depend on traditional roles in family or at work tend to oscillate with the level of depression, whereas functions that require personal initiative (e.g. leisure) may remain abnormal well into the interepisodic phase. The reported disturbances were especially marked in dysthymic or chronic depressives who seem to suffer from the long-term effects of depression.

A prospective study of stability and change over 2 years of affective temperaments in 14-18 year-old Italian high school students.

OBJECTIVE: It is generally accepted that temperament is not entirely stable, and that it changes with development, particularly in juvenile subjects; also, some temperaments are believed to be inherently more unstable. There is a great deal of current interest in Kraepelin's thesis that temperamental dysregulation in juvenile subjects represents the constitutional foundation from which the more florid episodes of manic-depressive illness arise; the cyclothymic, hyperthymic, depressive and irritable temperaments under consideration might represent the first observable phenotypes of the genetic diathesis for bipolarity. The analyses on the temperamental attributes in juvenile subjects were undertaken within this theoretical framework. METHOD: We evaluated 206 Italian high school students (14-18 years old) by means of a semi-structured affective temperament interview (TEMPS-I) at T0 and T1 two years later. Age, sex and psychometric properties of TEMPS-I raw scale score and weighted cut-off (as specially weighted linear combination of items) were used as predictive variables of stability. RESULTS: Affective temperaments had a low to moderate level of stability, reaching 60% in the case of subjects with dominant cyclothymic temperament. The stability of the depressive temperament was primarily related to its weighted cut-off. The stability of the hyperthymic temperament appeared related to male sex, young age, and total scale score. Male sex represented the best stability predictor for the cyclothymic temperament as well. The group of subjects with an unstable depressive temperament showed a change toward the dominant cyclothymic temperament, whereas individuals with unstable hyperthymic temperamental traits moved on towards the dominant cyclothymic and depressive temperaments. The irritable construct was the least stable. LIMITATIONS: The infeasibility of a multiwave design represents the main limitation in evaluating the predictors of stability. Furthermore, in the present analyses, the size of the cyclothymic subsample was small. CONCLUSION: Our data indicate considerable fluctuation and instability in depressive and hyperthymic temperaments in mid-adolescence. The cyclothymic temperament appears to be the most stable. Interestingly, cyclothymic moodiness appears more persistent in juvenile males; likewise persistent hyperthymic traits appear more of a "male" attribute. CLINICAL AND PUBLIC HEALTH IMPLICATIONS: We submit that these sex-relevant traits could be important in the risk of developing juvenile bipolarity. Literature review indicates that clinical studies, albeit on small samples, have already provided some support for this thesis. Larger studies on epidemiological samples could be more informative from a public health perspective. A user-friendly affective temperament questionnaire, which is under development, is critical for the methodology of such studies. Our study indicates that the present version of the Akiskal-Malya questionnaire can be easily used post-pubertally. Age adjustment must be considered for younger subjects.

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.

Differential changes in areas of social adjustment from depressive episodes through recovery.

The findings of the present short-term prospective study of 99 depressed outpatients further support previous cross-sectional observations to the effect that the course of depressive illness is often complicated by fluctuating social disturbances manifested by uneasiness in the work area, by disagreements with colleagues, and by difficulty in maintaining conflict-free relationships with significant others. By contrast, the incapacity to enjoy and use leisure time appeared less related to the symptomatologic variation in depression. Although we favor the hypothesis that impairment in leisure activity may represent a trait marker of depression, the hypothesis of it being a residual complication of repeated depressive episodes cannot be ruled out in view of short follow-up.

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.

Emotivity, personality, and task-dependent EEG asymmetry.

In order to verify if task-dependent EEG asymmetry is related to emotivity or personality traits, the relationship between EEGraphic (EEG mapping) asymmetry, personality aspects, and emotional-affective state in 12 healthy volunteers was evaluated by means of standardized methods (SAD and CPI). Our subjects show an EEG asymmetry which is currently attributed in the literature to anxiety. In our subject the absence of anxiety and the presence of hyperthymic characteristics suggests that the different individual trends observed in various studies which have used methods similar to ours, could, at least partly, depend on interference on these variables.

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.

High-affinity 3H-imipramine binding sites: a possible state-dependent marker for major depression.

Ten patients with DSM-III diagnoses of nonbipolar recurrent major depression were studied in an attempt to assess the relationship between 3H-imipramine binding site density and clinical depressive state. They were compared with eight healthy controls who had no past or family history of affective disorders. Evaluations with the Hamilton Rating Scale for Depression and the Self-Rated Scale for Depression were done on the same day as platelet collection at baseline, and also at 2 and 5 weeks after the beginning of treatment with tricyclic antidepressants. The number (Bmax) and the affinity (Kd) of platelet 3H-imipramine binding sites were highly correlated with the improvement of the clinical depression. These results raise the interesting possibility that a decrease in 3H-imipramine binding sites may be a state-dependent marker in patients suffering from nonbipolar recurrent major depression.

Controlled use of heroin in patients on methadone maintenance treatment.

The efficacy of methadone maintenance treatment was evaluated on 93 patients after 10 years of therapy. On the basis of therapeutic compliance, patients were divided into three groups: (a) 40 Total-Agreement subjects on weekly take-home methadone; (b) 28 Partial-Agreement subjects, who regularly attended the clinic daily but presented episodic positive urinalysis; (c) 25 No-Agreement patients, who were absent from the clinic more than twice a month and had a high rate of urinalysis positive for morphine. Statistical analysis, based on social adjustment improvement and criminality rate decrease, divided the 93 patients into 2 distinct categories. The first category, characterized by high social adjustment and low criminality score, included the Total- and Partial-agreement groups. The second, characterized by significantly lower social adjustment and higher criminality score, included all No-Agreement patients. This suggests that methadone treatment was able to dissociate heroin use from low social functioning. It was concluded that, in a condition of adequate compliance the episodic use of heroin is of no harm to patients on methadone maintenance therapy, that is, methadone maintenance treatment permits a controlled use of heroin.

The effectiveness of the combination fluoxetine-naltrexone in bulimia nervosa.

Four patients with DSM-IV bulimia nervosa were treated in a crossover trial with naltrexone alone, fluoxetine alone, and a fluoxetine-naltrexone combination. Three patients presented a complete remission when treated with the fluoxetine-naltrexone combination.