The future of precision medicine in opioid use disorder: inclusion of patient-important outcomes in clinical trials

Opioid use has reached an epidemic proportion in Canada and the United States that is mostly attributed to excess availability of prescribed opioids for pain. This excess in opioid use led to an increase in the prevalence of opioid use disorder (OUD) requiring treatment. The most common treatment recommendations include medication-assisted treatment (MAT) combined with psychosocial interventions. Clinical trials investigating the effectiveness of MAT, however, have a limited focus on effectiveness measures that overlook patient-important outcomes. Despite MAT, patients with OUD continue to suffer negative consequences of opioid use. Patient goals and personalized medicine are overlooked in clinical trials and guidelines, thus missing an opportunity to improve prognosis of OUD by considering precision medicine in addiction trials. In this mixed-methods study, patients with OUD receiving MAT (n=2,031, mean age 39.1 years [SD 10.7], 44% female) were interviewed to identify patient goals for MAT. The most frequently reported patient-important outcomes were to stop treatment (39%) and to avoid all drugs (25%). These results are inconsistent with treatment recommendations and trial outcome measures. We discuss theses inconsistencies and make recommendations to incorporate these outcomes to achieve patient-centered and personalized treatment strategies.

effects of gabapentin on methadone based addiction treatment: a randomized controlled trial

Gabapentin is a potentially useful drug in alleviating the hyperexcitatory painful states in the control of opiate dependence in acute detoxification and the stabilization phase. This study aim was to evaluate the effectiveness of gabapentin adds-on methadone therapy on lowering the methadone. This randomized double blind controlled clinical trial conducted at an outpatient rehabilitation clinic. Sixty patients using opium, opium extract and heroin were randomly assigned to two groups [34 in treatment group and 26 in control group]; one group was prescribed combination of methadone [40-120 mg] and gabapentin [300 mg] as group A, and the other group was given methadone [40-120] and placebo as group B. The subjects were followed up for three weeks after intervention. There were 60 outpatients including 51 males with the mean age of 40.9 +/- 9.2. Daily dose and cumulative dose of methadone during the treatment was found to be significantly higher in group B [73.8 +/- 19.5 mg daily vs. 58.9 +/- 11 mg daily and cumulatively 1550.7 +/- 409.7 mg vs. 238.3 +/- 238.2 mg, p= 0.001]. When the patients were stratified based on the kind of abused drug, the methadone dose was seen to be significantly reduced in the opium addicted patients in the group A. Group A showed more withdrawal symptoms whereas the most common complain of group B was sedation particularly during the first three days. The results showed that gabapentin is an effective adds-on therapy when is added to methadone. This drug leads to relief of withdrawal symptoms and lower methadone consumption

Dual addictions, parallel treatments: nicotine replacement therapy for patients receiving methadone treatment in the Islamic Republic of Iran

This parallel, randomized, open-ended clinical trial tested the impact of nicotine replacement pharmacotherapy during the course of methadone treatment among opiate abusers. A total of 424 men entered the study at 4 drug treatment centres in Tehran, Islamic Republic of Iran. The intervention group received a 6-week regimen of nicotine replacement pharmacotherapy at no charge. After 6 months, 211 persons [99.5%] in the control group continued to smoke and 1 person [0.5%] had quit. In the intervention group, 117 [55.1%] persons smoked, 15 [7.1%] persons had quit and 80 [37.7%] had reduced by more than 50% the number of cigarettes they smoked at the start of the study [P < 0.0001]. The findings suggest that the use of nicotine replacement pharmacology in tandem with methadone maintenance treatment can lead to dramatically improved efficacy for treatment of dual addictions

Comparative study of verapamil and thioridazine in acute opioid abstinence syndrome

To determine the effectiveness of verapamil and thioridazine in the treatment of acute opioid withdrawal syndrome in patients with chronic dependence on opioids. The study was conducted at Psychological Medicine Ward, Civil Hospital Karachi and Arshi Hospital, Naseerabad, F.B. area Karachi. A total of forty [40] patients were admitted for ten [10] days in hospital. No treatment was given during the first two days of admission after abrupt termination of opioid to observe the acute opioid withdrawal signs and symptoms. Patients were divided into 2 groups. Each group comprising of 20 opiate addicts. One group was given verapamil orally in a 40mg dose thrice daily and the other group was given thioridazine orally in a 10mg dose thrice daily from day 3 to day 9 of admission. The intensity of sign and symptoms were recorded by using subjective and objective opiate withdrawal questionnaire. Urine analysis for opioids was done on day 1, 5 and 10 of admission. Verapamil in comparison to thioridazine significantly decreased admission. Urine analyses for opioids were positive on day 01 while zero on day 10. Verapamil in comparison to Thioridazine was found to be safe and effective for the treatment of signs and symptoms of acute opioid withdrawal in in-door patients without any significant side effect

Diretrizes para o tratamento de pacientes com síndrome de dependência de opióides no Brasil / Brazilian guideline for the treatment of patients with opioids dependence syndrome

Existe uma prevalência relativamente baixa do uso de ópioides no Brasil, em particular envolvendo o uso não médico da codeína e de xaropes que contêm opióides. No entanto, a síndrome de dependência apresenta um significativo impacto total na mortalidade e morbidade. Nos últimos 20 anos, o avanço científico tem modificado nosso entendimento sobre a natureza da adição aos opióides e os variados tratamentos possíveis. A adição é uma doença crônica tratável se o tratamento for realizado e adaptado tendo em vista as necessidades do paciente específico. Há, de um fato, um conjunto de tratamentos que podem efetivamente reduzir o uso da droga, ajudar a gerenciar a fissura pela droga, prevenir recaídas e recuperar as pessoas para o funcionamento social produtivo. O tratamento da dependência de drogas será parte de perspectivas de longo prazo do ponto de vista médico, psicológico e social. Esta diretriz almeja fornecer um guia para os psiquiatras e outros profissionais de saúde que tratam de pacientes com Síndrome de Dependência de Opióides. Ela tece comentários sobre o tratamento somático e psicossocial que é utilizado nesses pacientes e revisa as evidências científicas e seu poder. Da mesma forma, os aspectos históricos, epidemiológicos e neurobiológicos da dependência de opióides são revisados.

Pharmacotherapies of addiction

Millions of drug addicts worldwide require proper treatment together with good quality care. This article aims to critically review the psychopharmacology of drug addictions. MEDLINE was systematically searched for studies describing drug treatment of addictions. Numerous studies were obtained and grouped according to the drug used to treat addictions. Although there are many effective antiaddictive drugs in the therapeutic armamentarium of drug addictions, a great number of patients tend to develop poor drug compliance, multiple relapses, and continue to suffer from chronic addictions coupled with negative biopsychosocial consequences. Aside from enhancing the public awareness of the devastating effects of drug addictions through regular and effective mass media campaigns, scientific efforts should be continued in order to develop new antiaddictive drugs with better clinical profiles for the treatment of patients with addictions

Role of clonidine in acute opioid abstinence syndrome

Recently clonidine has been used in opioid abstinence syndrome. It is proposed that, norepinephrine is involved in the expression of abstinence syndrome, and it depends upon the cerebral stores of these catecholamines. The effects of activation of locus coeruleus was demonstrated to produce changes that resembled those seen in opiate withdrawal. Hence this study was conducted to observe the effects of clonidine on acute opioid abstinence syndrome. Setting: Twenty healthy, opiate-dependent patients were selected randomly, who were seeking inpatient opioid abstinence treatment. This study was conducted in single blind protocol. Clonidine 300mcg/day was given. All patients completed the treatment program and stayed in the hospital for 10 days. Clonidine showed a very rapid and highly significant decline in the objective signs and subjective symptoms of opiate withdrawal syndrome. Clonidine proved to be highly effective non-opioid treatment of acute opioid withdrawal syndrome. This observation indicates that opioid withdrawal syndrome may be due to increased neural activity in locus coeruleus, which is regulated by both alpha-2 adrenergic and opiate receptors