Childhood abuse and treatment response in patients with irritable bowel syndrome: a post-hoc analysis of a 12-week, randomized, double-blind, placebo-controlled trial of paroxetine controlled release.

OBJECTIVE: Although irritable bowel syndrome (IBS) is frequently comorbid with childhood trauma, information on the clinical implications of this comorbidity is limited. We investigated whether a history of abuse was associated with response to treatment in a double blind, randomized, placebo controlled trial of paroxetine controlled release (CR) in IBS. METHODS: Seventy-two IBS subjects were randomized to receive paroxetine CR (dose 12.5-50 mg/day) or placebo for 12 weeks. Subject selection was independent of abuse history. Sixty-one subjects completed the Sexual and Physical Abuse Questionnaire about their childhood abuse history. IBS symptoms were recorded using the Interactive Voice Response System (IVRS). Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Perceived Stress Scale (PSS) and Clinical Global Impression (CGI) were also measured. The primary outcome was treatment response defined as > or =25% reduction in composite pain scores (CPS) on the IVRS from randomization to end of treatment. RESULTS: The rate of abuse history was 50.8% (n = 31/61). Baseline demographic clinical characteristics (CPS, BDI, BAI, PSS, CGI scores) were not associated with abuse history. After 12 weeks of treatment, subjects with abuse history showed significantly higher CPS (t = 2.422, P = 0.018) than subjects without a history and less mean change of CPS (t = 3.506, P = 0.001). In a logistic regression analysis, history of abuse did not predict treatment response as measured by > or =25% reduction in CPS (OR = 0.481, CI = 0.164-1.406, P = 0.181), while the drug status (paroxetine CR) was significantly associated with treatment response as defined by a CGI improvement score of 1-2 (OR = 12.121, CI = 2.923-50.271, P = 0.001). Abuse history did not predict CGI-I (Fisher's exact, P = 0.500) improvements during the trial. CONCLUSIONS: History of abuse did not appear to have any significant clinical correlates at baseline and did not predict treatment response. Further studies are needed to confirm whether SSRIs are effective in IBS patients irrespective of their abuse history.

Serendipitous rapid detoxification from opiates: the importance of time-dependent processes.

Opiate detoxification procedures aim to reduce intensity and duration of withdrawal. Ultra-rapid opiate detoxification (UROD) methods attempt to obtain this goal by administering naltrexone under deep sedation or anaesthesia. We present a case study on accidental ingestion of naltrexone in a methadone maintenance patient, which shows close methodological similarities with UROD procedures. Naltrexone was effective in reducing withdrawal duration, but not as much as UROD studies report. The administration of naloxone after detoxification did not trigger withdrawal symptoms, even in the presence of methadone, as detected by urinalyses. These results suggest the importance of further developing detoxification methods based on protocols of administration of antagonists different from UROD, in absence of anaesthesia.

Opiate detoxification of methadone maintenance patients using lefetamine, clonidine and buprenorphine.

Thirty-nine methadone maintenance patients were included in a 9-day, double blind, randomized, inpatient detoxification trial. Methadone was tapered to 10 mg/day and then patients were assigned to one of these 3 protocols: clonidine (0.3-0.9 mg/day), lefetamine (60-240 mg/day), buprenorphine (0.15-0.9 mg/day). Buprenorphine treatment was significantly superior to clonidine and to lefetamine (F = 3.96 df = 2, 29 P < 0.05) in controlling objective, subjective and psychological withdrawal symptomatology. Clonidine was more effective than lefetamine in suppressing withdrawal in the first 3 days of treatment (day 3: F = 4.10 df = 2, 30 P < 0.05), and this trend was apparent on the objective and psychological items. In addition to evaluations of the efficacy of the single drugs used, the study showed that tapering methadone to low doses before entering the pharmacologically assisted discontinuation phase was clinically acceptable in detoxification from long-term methadone treatment.

Lefetamine: new abuse of an old drug--clinical evaluation of opioid activity.

Lefetamine (SPA) combining amphetamine with opioid-like effects, a drug of wide abuse in Japan in the fifties, has now been introduced as such in Italy. In this study the drug was tested to verify its resemblance to opiates. Ten lefetamine abusers were hospitalized and then subjected to naloxone- and pentazocine-tests and detoxified. Moreover, lefetamine was administered to ten opiate addicts with an acute withdrawal syndrome and to ten methadone-treated addicts. The naloxone-test was positive and pentazocine could be substituted for lefetamine. Lefetamine was able to relieve opiate withdrawal and did not precipitate withdrawal symptoms in stabilized opiate addicts. It is concluded that lefetamine may act as an opioid partial agonist.

Zipeprol is a newly abused antitussive with an opioid spectrum and hallucinogenic effects.

Zipeprol is a non-opioid cough suppressor agent recently abused in Italy. Clinical reports from 30 street abusers show that the drug in high doses has a definite abuse liability and dependence potential. Many of its effects were identical to those induced by opiates, although specific dysperceptive symptoms were commonly reported by patients. Spontaneous withdrawal symptoms were similar to those of opiates. Withdrawal could be also precipitated by naloxone. It is concluded that zipeprol can induce dependence with a mechanism which may be mediated by some types of opioid receptors.

Effects of fluoxetine at antidepressant doses on short-term outcome of detoxified alcoholics.

Compulsivity in alcohol-dependent patients is a frequent cause of early relapse in the post-detoxification period. The present study is a 2-month trial on detoxified alcoholics undergoing a double-blind placebo-controlled treatment with fluoxetine (20 mg/day). The rating instruments were the Hamilton Depression and Anxiety Scales, a visual analogue scale for alcohol craving and an original scale for evaluating alcohol withdrawal. The abstinence rate for fluoxetine-treated patients was significantly higher than in the placebo group, whereas no difference between treatments was found on the rating scales. Medical problems, additional psychiatric diagnoses, and family alcoholism were negatively correlated with abstinence. Two subgroups of patients having significantly different characteristics were identified as to the outcome, by means of cluster analysis. They are likely to represent two different stages in the evolution of alcoholism. Our results show that, independently from craving, fluoxetine at antidepressant doses is able to prevent relapses in weaned alcoholics. The anticompulsive therapy can positively influence the short-term outcome, while other factors are negatively associated with abstinence.

Psychological discomfort and mental illness in patients with AIDS: implications for home care.

A chart review study of 100 consecutive AIDS patients cared for by our Home Care (HC) unit was performed. The main characteristics of the sample were: M/F ratio = 3/1; mean age = 39.7 +/- 6.6; mode of transmission = 56% intravenous drug users (IVDU); Centers For Disease Control (CDC) classification = 98% C3; mean length of HC = 5.2 months. Psychopathological evaluation led to an overall rate of morbidity during HC of 73%. The most common psychiatric diagnoses were dementia and adjustment disorders. Nearly two thirds of the patients received psychopharmacological treatment; one fifth were still on methadone. Psychological discomfort was perceived by more than half of patients. Interpersonal problems with cohabitants were noticed by caregivers in 41%. Female patients showed an increased prevalence of anxiety and depressive disorders. IVDUs had more prominent psychosocial problems. Interpersonal problems with cohabitants were correlated to substance use or other mental disorders in the family and to the patient's psychological discomfort. We conclude that mental health professional intervention for AIDS patients is strongly needed in a home-care setting.

Emergency therapeutical approach simulating ultrarapid opioid detoxification in methadone withdrawal precipitated by erroneous administration of naltrexone.

We report the case of a 30-year-old male, heroin dependent, receiving methadone treatment, who, while staying at home, ingested 50 mg of naltrexone. He immediately developed serious withdrawal symptoms and was admitted to the hospital. In the emergency department the drugs given to counteract the agitation were ineffective, and the patient developed respiratory distress. Anaesthesia with propofol was then started and the patient was intubated, ventilated and hospitalized in the intensive care unit. He was then sedated for 48 hours due to persistent withdrawal signs. When medically stable the patient was transferred to the medical ward where daily treatment with naltrexone and psychological support where started. After 4 days the patient was discharged. Afterwards he did not attend his scheduled outpatient follow-up visits. Treatment with propofol is effective in the case of a patient with a serious withdrawal syndrome secondary to naltrexone overdose during methadone therapy. Despite the actual possibility of getting through the withdrawal symptoms the patient failed to return for follow-up visits, which might be related to a lack of motivation.

Prediction in drug abuse: cocaine interactions with alcohol and buprenorphine.

We describe the limitations on studying the interactions of drugs of abuse in humans. Two 'acute' studies were carried out. In the first study, the administration of alcohol/placebo with cocaine showed the possibility of identifying the euphoric effect of the drugs by the EEG power spectra analysis in terms of enhancement of alpha- and beta-wave activity. The results of the second study, in which cocaine and buprenorphine were administered, show the existence of low-dose interactions and the influence of buprenorphine on craving for cocaine.

Agonist-antagonist combinations in opioid dependence: a translational approach.

The potential therapeutic benefits of co-administering opiate agonist and antagonist agents remain largely to be investigated. This paper focuses on the mechanisms of very low doses of naltrexone that help modulate the effects of methadone withdrawal and review pharmacological properties of the buprenorphine/naltrexone combination that support its clinical investigation. The bench-to-bedside development of the very low dose naltrexone treatment can serve as a translational paradigm to investigate and treat drug addiction. Further research on putative mechanisms elicited by the use of opioid agonist-antagonist combinations may lead to effective pharmacological alternatives to the gold standard methadone treatment, also useful for the management of the abuse of non opioid drugs and alcohol.

Elevated mu-opioid receptor expression in the nucleus of the solitary tract accompanies attenuated withdrawal signs after chronic low dose naltrexone in opiate-dependent rats.

We previously described a decrease in withdrawal behaviors in opiate-dependent rats that were chronically treated with very low doses of naltrexone in their drinking water. Attenuated expression of withdrawal behaviors correlated with decreased c-Fos expression and intracellular signal transduction elements [protein kinase A regulatory subunit II (PKA) and phosphorylated cAMP response element binding protein (pCREB)] in brainstem noradrenergic nuclei. In this study, to determine whether similar cellular changes occurred in forebrain nuclei associated with drug reward, expressions of PKA and pCREB were analyzed in the ventral tegmental area, frontal cortex, striatum, and amygdala of opiate-treated rats that received low doses of naltrexone in their drinking water. No significant difference in PKA or pCREB was detected in these regions following drug treatment. To examine further the cellular mechanisms in noradrenergic nuclei that could underlie attenuated withdrawal behaviors following low dose naltrexone administration, the nucleus of the solitary tract (NTS) and locus coeruleus (LC) were examined for opioid receptor (OR) protein expression. Results showed a significant increase in muOR expression in the NTS of morphine-dependent rats that received low doses of naltrexone in their drinking water, and increases in muOR expression were also found to be dose dependent. Protein expression of muOR in the LC and deltaOR in either brain region remained unchanged. In conclusion, our previously reported decreases in c-Fos and PKA expression in the NTS following pretreatment with low doses of naltrexone may be partially explained by a greater inhibition of NTS neurons resulting from increased muOR expression in this region.

Lephetamine abuse and dependence: clinical effects and withdrawal syndrome.

Lephetamine (L-SPA) is a compound with central analgesic and anti-inflammatory action, recently reported to be abused in Italy. In this study, cases of L-SPA abuse were recorded. The survey included 15 patients who were assessed for effects caused by using L-SPA and induced by withdrawal. Moreover L-SPA was administered to 15 volunteers. L-SPA displayed effects partly similar to opiates and its withdrawal caused both subjective and objective symptoms. It is concluded that L-SPA exhibits abuse liability and dependence potential of a certain degree.

Adjuvant trazodone in the treatment of alcoholism: an open study.

Serotonergic drugs have been proven to be helpful to alcoholics in maintaining abstinence. In this open study, we report that the atypical antidepressant trazodone at low doses was able to significantly decrease craving for alcohol, depressive, and anxious symptoms in a number (25) of detoxified alcohol-dependent subjects after 3 months of treatment. Trazodone may, therefore, be an adjuvant in the therapy of alcoholism.

[Benzodiazepines consumption and risk of dependence in institutionalized geriatric patients]. / Consumo di benzodiazepine e rischio di dipendenza in pazienti geriatrici istituzionalizzati.

The use of psychoactive drugs in geriatric nursing homes has to be considered within the peculiar frame work of the elderly condition. The present study was aimed at verifying the prevalence and characteristics of prolonged benzodiazepine use (greater than 1 month) in the entire elderly institutionalized population of an Italian region (Molise). In the 31 benzodiazepine consumers identified, psychosocial and clinical data were recorded by means of a specific scale and of a semistructured interview for the assessment of drug effects. The dependence potential was evaluated in a smaller sample of 18 patients, recording with a scale the onset of withdrawal and/or rebound symptoms following discontinuation of drug treatment. The characteristics of prescription appeared to be generally correct and no appreciable tendency toward abuse was evidenced. In only one patient, discontinuation of benzodiazepines precipitated a confusional state. In other 5 patients significant but not severe withdrawal symptoms were recorded. Duration of treatment was the only variable moderately correlated with the onset of withdrawal/rebound symptomatology (p less than 0.1). In conclusion, the results of our study are reassuring but they should not induce to disregard important clinical aspects of psychopharmacotherapy in the elderly, such as: psychopathological diagnosis, drug associations and interactions, duration of treatment and dosage of prescribed benzodiazepines.