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23УДК 616.89
НОВЫЕ ПОДХОДЫ К ЛЕЧЕНИЮ ОПИОДНОЙ ЗАВИСИМОСТИ
Звонарев Валерий Владимирович.
Москва, Федеральное государственное автономное образовательное учреждение высшего образования Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский Университет), zvonarevv@mail.ru
Аннотация. Опиоидная зависимость от лекарств и запрещенных наркотиков является серьезной и растущей проблемой. Эта мировая проблема затрагивает социальное, медицинское и экономическое благосостояние общества [1]. Несмотря на эту распространенность, почти 80% лиц, страдающих зависимостью, остаются без лечения. Кроме того, ограничительные государственные нормы и стереотипы о опиоидной зависимости и лечении ограничили доступность новых вариантов лечения.
В настоящее время для решения проблемы используются различные способы обучения пациентов, чтобы избежать чрезмерного употребления опиатов.
В статье представлена эпидемиология злоупотребления опиоидами, рассмотрены существующие лекарства, используемые для терапии, и освещены несколько новых вариантов лечения.
Мы проанализировали недавние доклады о программах лечения и о том, как они эффективны при лечении расстройств опиоидного использования. Мы рассмотрели и проанализировали основные принципы каждой исследовательской программы лечения: структуру, содержание и доставку.
Используемый метод включал систематический анализ новых данных и последних исследований Национального института злоупотребления наркотиками (США). Мы исследовали онлайн-источники и базы данных до сентября 2017 года. Окончательный результат данного анализа показал, что новые исследования и программы лечения эффективны в снижении зависимости.
Ключевые слова: наркомания, опиоид, исследования, бупренорфин, вакцина, tDCS, семейная терапия, паннексин.
NEW APPROACHES TO OPIOID ADDICTION TREATMENT
Valeriy Zvonarev.
Sechenov University, Moscow, Russia, zvonarevv@mail.ru
Abstract. Opioid addiction to prescribed and illicit drugs is a serious and growing problem. This world problem affects social, health and economic welfare of the society [1] Despite this prevalence, nearly 80% of opioid-dependent people remain untreated. Also, restrictive state regulations and stereotypes about opioid addiction and treatment have limited the availability of new treatment options.
Currently, multifaceted ways of educating patients are being used to solve the crisis and to avoid overuse of opiates.
This review introduces the study of opioid abuse, examines existing medications used for therapy, and highlights several new treatment options.
We analyzed recent reports on treatment programs and their efficiency in treating opioid usage disorders. We considered and analyzed the following major principles of each research-based treatment programs: structure, content and delivery.
The method involved systematic analysis of new data and most recent studies from National Institute of Drug Abuse (USA) and CDC. We searched MEDLINE®, clinicaltrials.gov, ncbi.nlm.nih.gov and other online sources and databases through September 2017. The final result of this analysis showed that new studies and treatment programs have been effective in reducing drug addiction.
Key words: addiction, opioid, studies, buprenorphine, vaccine, tDCS, family therapy, pannexin.
Current Problems in Treatment of Opioid Addiction.
Even though it does not have the highest level of opioid utilization globally, Russia has a considerable issue with the abuse of opioids. To date, a significant number of Russian citizens are battling an addiction to opioids with minimal to no resources for therapy. An approximated 100,000 Russians lose their lives to the use of opioids every year. 1However, this number might be even bigger as the Russian government is not exceedingly transparent concerning addiction in the nation. Russia faces a looming problem in the treatment of opioid addiction: in a nation with the biggest populace of inoculation drug users, methadone treatment is prohibited. The opiate addicts in Russia struggle to deal with stigmatization at an official, government level and often face unscientific therapy plans. The public outlook is exceedingly antagonistic, and the administration does not want to appear too gentle towards drug addicts. Moreover, the government is not committed to funding scientific investigations concerning the treatment of opioid addiction. Ideally, opioid addicts, who are considered as antisocial elements by the government are expected to relinquish maybe in one of the prison-like therapy centers. Russia also bans peer-reviewed pharmacological substitution therapies preferred by the global public health community along with methadone clinics.
Evidence reveals that several methods are efficient when it comes to treatment of addiction to opioids [1]. However, in some way, these treatment strategies are victims of their success given the fact that they have been associated with some problems which have the capacity of deterring the ability of patients to heal [4]. Medication-assisted therapies (MAT) are related to challenges which hinder completion of the treatment regimen. Even though oral route has been a primary treatment method, it is associated with problems relating to compliance and overdosing. Many studies have supported the efficacy of buprenorphine in opioid withdrawal. However, even with the advantages linked to buprenorphine, the possession of the medication in the hands of patients has inevitably resulted in some illegal usage and diversion to individuals not under medical care [1]. Therefore, buprenorphine can be abused and is currently being used illicitly. Another major contributor to the current opioid epidemic is the pharmaceutical advertising and prescription practices [7]. The prescribing guidelines produced by the
CDC accentuate that there should be general avoidance of opioid prescriptions for chronic nonmalignant pain. If an opioid is deemed necessary, the providers are required to start slow and go low. [8]
Overview of New Studies in Opioid Addiction Treatment
New generation of buprenorphine implants
Examination of the long-acting implant form of buprenorphine reveals that the delivery method has efficacy. Data were collected from 18 US through a 6 month randomized placebo-controlled trial which used 163 opioid-dependent adults aged between 18 to 65 years as the participants. After being induced with sublingual buprenorphine/naloxone, four 80 mg buprenorphine implants were given to 108 participating patients while four placebo implants were given to 55 patients. Additionally, all patients received individualized drug counseling. [4]The study then examined the percentage of negative urine samples for illicit opioids across 1-16 weeks. Compared to the placebo group which recorded a 28.3% of negative specimens, the implant group has high rates of negative samples (P=0.04); a mean of 40.7%. Similarly, the implant group reported fewer clinician related withdrawal (P<0.001) and patiently related withdrawal (P=0.004). Also, this group reported higher global ratings by improvements of physicians (P<0.001). However, there were merely minor reactions at the implant sites which were reported for both groups. Therefore, this work provided more evidence which proved that safety and efficacy of buprenorphine.
A review of a study conducted by Rosenthal included 177 patients who were previously clinically stable on <8 mg of sublingual buprenorphine/naloxone. These patients were enrolled for maintenance therapy double-blind Phase III study of the Probuphine implant which lasted for 24 weeks. Within six months, 90 patients have received placebo implants with a daily sublingual form of buprenorphine while 87 patients were randomly assigned to receive four 80 mg buprenorphine implants with placebo sublingual Probuphine tablets. The study refines the participants to have abstained from illicit opioid use for four and more months out for the six months as revealed by the tests done on the urine samples as self-reports. The sublingual group had more responders (87.6%) compared to the Probuphine arm (96.4%). A considerably greater number of responders in the Probuphine arm remained abstinent from opioid abuse compared to the sublingual. Therefore, from the above findings; it is evident that Probuphine implant has the potential to improve patient's life quality. [4] Buprenorphine implant offers steady drug amounts for up to 6 months while also diminishes the sensations of highs and lows often associated with abuse and withdrawal. Therefore, this property allows the medication to assist in overcoming the challenge of patients missing doses and hence allows for more consistency with MAT.
Cocaine Vaccine.
A vaccine developed to prevent cocaine abuse and addiction proved mildly useful in the first placebo-controlled test. When compared to the placebo recipients, the vaccine recipients reduced their cocaine use more quickly. The vaccinated patients generated levels of antibodies sufficient to block the effects of cocaine. [9] The group submitted more drug-free urine samples in comparison to the placebo group during the peak antibody production. The cocaine vaccines consist of drugs that stimulate the production of antibodies within the immune system. The anti-cocaine antibodies
produced latch onto the cocaine molecules and form drug antibody complexes which cannot pass through the fine-grained tissue filter that enwraps and protects the brain due to their large sizes.
The patients who received the vaccine and placebo both reduced their cocaine use with the former doing so more rapidly. There was generate variation on the antibody responses amongst the vaccinated patients with only 38% of the 55 who completed the injection series produced antibodies in the quantity that will be successful in blocking drug-induced euphoria. The vaccine group provided cocaine free urine samples 45% of the time during the eight weeks of the greatest antibody response. 53% of the patients who produced euphoria blocking antibody levels doubled the regularity, with which their urine samples demonstrated no new cocaine use. Therefore, with the vaccine, approximately 70% of cocaine abusers have the potential of developing antibody which will block the euphoric effect of cocaine by more than 90%. This effect is sufficient to prevent relapse in most individuals.
Neuromodulation for addiction by transcranial direct current stimulation.
Transcranial direct current stimulation (tDCS) has been used for the successful treatment of various ailments and disorders in the clinical field. Non-invasive brain stimulation (NIBS) is a method used to modulate the activity in the brain. tDCS is a NIBS technique and has emerged as a non-invasive tool for modulating the excitability of the cortex.
It is believed that tDCS might be a reasonable alternative treatment for addiction. tDCS still face various challenges in spite of the advances related to it. There is a need for the establishment of optimal tDCS stimulation configurations and protocols for different cortical regions.
Blocking microglial pannexin-1 channels alleviates morphine withdrawal.
This research administered an opioid receptor antagonist to investigate the mechanisms which underlying opiate withdrawal. The investigation was carried out on rats chronically treated for 5 d with systemic morphine sulfate. The administration of Naloxone revealed a range of autonomic and somatic withdrawal signs in the rats treated with morphine but not those treated with saline. Amongst the rats treated with morphine, there was the significant elevation of immunoreactivity within the spinal dorsal horn. Therefore, it indicated that morphine treatment activated the spinal microglia. The decrease of withdrawal behaviors and attenuation of the severity of withdrawal came about due to the exhaustion of lumbar spinal microglia by intrathecal injections of a saporin.
In conclusion, this study has been able to recognize the pannexin-1 (Panx1) channel as a therapeutic target in opiate withdrawal. The study revealed that there was the induction of long-term synaptic facilitation in lamina I and II neurons when there is withdrawal from morphine. The spinal synaptic facilitation and ameliorated the sequelae of morphine withdrawal was abolished by the genetic ablation of Panx1 in microglia. Additionally, this study can demonstrate that the activation of Panx1 drives the release of ATP from microglia during morphine withdrawal. This degrades endogenous spinal ATP through the administration of apyrase which then produces a reduction in withdrawal behaviors. Suppression of the release of ATP and reduction of withdrawal severity is achieved through treatment with a Panx1-blocking peptide or the
clinically used broad-spectrum Panx1 blockers, mefloquine or probenecid.
Success of family therapy for adolescents who abuse drugs.
From the study, it is evident that a year after treatment, the teenagers who were treated with multidimensional family therapy (MDFT) had fewer drug-related issues. Furthermore, these adolescents showed signs of more improvement on general measures of behavior and mental health compared to those teens treated with cognitive behavioral therapy (CBT). CBT focuses on an individual and not a family but just like MDFT aims to equip parents with skills which they can use to reduce drug abuse and also cope with problems which come from different areas of life.
This study was set on a community-based drug abuse clinic. The participants were 224 youths who were predominantly African American males with an average age of 15 years. 75% of the participants were found to mostly abuse cannabis. 20 percent were dependent on alcohol while 13 percent were dependent on other substances. Half of the group was randomly assigned to MDFT while the remaining half CBT. At the end of the therapy, it was evident that both CBT and MDFT were similarly effective. By the last month of the research, use of cannabis amongst the two groups had significantly dropped.
The results revealed that both studies were useful at discharge. However, the recipients of MDFT experienced gains which lasted longer.
Conclusion.
The problem of opioid abuse in Russia has become increasingly common mainly because of the collapse of Russia's public health scheme. Many people in the country are addicted to the various forms of opioid, and as a result, many deaths have also been experienced. Furthermore, it has resulted in various public health concerns including suicide, deaths, pregnancy, and HIV and hepatitis infections. Nonetheless, users in the country suffer from immense stigmatization at an official, government level and often face unscientific therapy plans. While these are the cases, there is the need for Russia to step up in regards to controlling drug use in the country lest the nation will fall deeper into this menace. In any case, the country should begin using other methods of treatment to assist addicts.
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