Protracted Withdrawal Symptoms Research Articles

Effects of CB1 receptor negative allosteric modulator Org27569 on oxycodone withdrawal symptoms in mice.

Targeting cannabinoid receptor type 1 (CB1R) has shown promise for treating opioid withdrawal symptoms. This study aimed to investigate the efficacy of a specific CB1R negative allosteric modulator (NAM), Org27569, in reducing both naloxone-precipitated and protracted withdrawal symptoms in oxycodone-dependent mice. Mice received escalating doses of oxycodone (9-33mg/kg IP) or saline twice daily for 9 days, followed by a final dose of oxycodone (33mg/kg) or saline in the morning of day 9. In one cohort, the impact of Org27569 (3, 10, and 30mg/kg) on naloxone (10mg/kg IP) precipitated withdrawal symptoms was assessed. In another cohort, Org27569 (3mg/kg) effects on the acquisition of conditioned place aversion to naloxone (0.6mg/kg) precipitated opioid withdrawal, on behaviour following a 7-9-day abstinence period, and on naloxone (0.6mg/kg) precipitated withdrawal-induced escape behaviour in a novel assay were assessed. Although Org27569 decreased opioid withdrawal-induced jumping at doses of 10 and 30mg/kg, these effects were confounded by reduced locomotion. At all doses tested, Org27569 had a modest inhibitory effect on gastrointestinal motility. At the lower dose of 3mg/kg, which was not confounded by locomotor effects, Org27569 did not impact naloxone-precipitated withdrawal-induced jumping, acquisition of oxycodone withdrawal-induced conditioned place aversion, or naloxone-precipitated withdrawal-induced escape behaviour in a novel assay. A clear protracted opioid withdrawal phenotype was not observed in assays of anxiety-like or social behaviour. Org27569 effects on negative affective-like symptoms were confounded by locomotor effects and effects on gastrointestinal motility were not opioid withdrawal specific. Further studies are needed in a model that produces a more pronounced protracted withdrawal syndrome.

Pain in alcohol use disorder: Evaluating effects of childhood trauma, perceived stress, and psychological comorbidity

The relationship between pain and alcohol use disorder (AUD) is complex and bidirectional. The current study examines risk factors for pain in a large comprehensively phenotyped sample including individuals from across the spectrum of alcohol use and misuse. Participants (n = 1101) were drawn from the National Institute on Alcohol Abuse and Alcoholism Natural History Protocol and included treatment-seeking AUD inpatients (AUD+Tx, n = 369), individuals with AUD not seeking treatment (AUD+, n = 161), and individuals without AUD (AUD-, n = 571). General linear models were utilized to test the effects of AUD status, history of childhood trauma exposure, perceived stress, and psychological comorbidity on daily percent time in pain, as well as change in daily percent time in pain across the inpatient stay in AUD+Tx individuals. Overall, 60.2% individuals reported any pain, with a significantly higher prevalence in the AUD+Tx group (82.1%) compared to the AUD+ (56.5%) and AUD- (47.1%) groups. Daily percent time in pain was also highest in the AUD+Tx group (30.2%) and was further increased in those with a history of childhood abuse and comorbid posttraumatic stress disorder (PTSD). Years of heavy drinking and craving were also associated with increased percent time in pain in the AUD+Tx group. Percent time in pain decreased following acute withdrawal in the AUD+Tx group but plateaued around 25% just prior to discharge. Individuals seeking inpatient treatment for AUD, especially those with a history of childhood trauma and/or comorbid PTSD, report greater percent time in pain compared to those not seeking treatment and those without AUD. The prolonged experience of pain in abstinent AUD inpatients after the resolution of acute withdrawal may signal the early stages of protracted withdrawal. Integrative treatments targeting pain and other symptoms of protracted withdrawal may be effective in improving overall function in people with severe AUD.

Acupuncture for protracted opioid abstinence syndrome: study protocol for a systematic review and meta-analysis

IntroductionProtracted opioid abstinence syndrome (POAS) refers to a series of physical discomforts and neuropsychiatric symptoms after discontinuation of opioid-type substances for a certain amount of time and is one of...

Enduring neurological sequelae of benzodiazepine use: an Internet survey.

Benzodiazepine tapering and cessation has been associated with diverse symptom constellations of varying duration. Although described in the literature decades ago, the mechanistic underpinnings of enduring symptoms that can last months or years have not yet been elucidated. This secondary analysis of the results from an Internet survey sought to better understand the acute and protracted withdrawal symptoms associated with benzodiazepine use and discontinuation. An online survey (n = 1207) was used to gather information about benzodiazepine use, including withdrawal syndrome and protracted symptoms. The mean number of withdrawal symptoms reported by a respondent in this survey was 15 out of 23 symptoms. Six percent of respondents reported having all 23 listed symptoms. A cluster of least-frequently reported symptoms (whole-body trembling, hallucinations, seizures) were also the symptoms most frequently reported as lasting only days or weeks, that is, short-duration symptoms. Symptoms of nervousness/anxiety/fear, sleep disturbances, low energy, and difficulty focusing/distractedness were experienced by the majority of respondents (⩾85%) and, along with memory loss, were the symptoms of longest duration. Prolonged symptoms of anxiety and insomnia occurred in many who have discontinued benzodiazepines, including over 50% who were not originally prescribed benzodiazepines for that indication. It remains unclear if these symptoms might be caused by neuroadaptive and/or neurotoxic changes induced by benzodiazepine exposure. In this way, benzodiazepine withdrawal may have acute and long-term symptoms attributable to different underlying mechanisms, which is the case with alcohol withdrawal. These findings tentatively support the notion that symptoms which are acute but transient during benzodiazepine tapering and discontinuation may be distinct in their nature and duration from the enduring symptoms experienced by many benzodiazepine users.

The Withdrawal After the Withdrawal: Managing Benzodiazepine Reduction and Post-Acute Withdrawal in Older Adults

<h3>Introduction</h3> Post-acute withdrawal, also described as protracted, extended or persistent withdrawal, refers to a syndrome that includes anxiety, irritability, hostility, mood instability, fatigue, insomnia and increased physical complaints often related to gastrointestinal symptoms, pain and weakness. Unlike acute withdrawal, where treatment guidelines and practices are highly predictable and protocol driven; post-acute interventions are highly symptom driven and individualized. Attention to co-occurring medical and psychiatric disorders is vital as well. It is well-known that benzodiazepines pose greater risks to older adults including confusion, ataxia, syncope, risk of falls, fractures, delirium and excess hospitalizations. Even with these known risks about 20-25% of all inappropriate prescriptions for benzodiazepines are given to older adults. There is limited literature on managing post-acute withdrawal syndromes in older adults, with few available guidelines for medication management of emerging symptoms. The additional challenges of the COVID-19 pandemic have increased both the stress on older adults in need of care and of providers seeking to engage patients in therapeutic relationships. We focus on representative cases of older adults seeking treatment related to benzodiazepines withdrawal and describe flexible treatment approaches for their evolving and complex needs. <h3>Methods</h3> Cases studies were identified from the patient population at Mount Sinai Beth Israel, an urban medical center serving a multicultural and socioeconomically diverse population that includes several NORC sites. Mount Sinai Beth Israel has been serving the population of lower Manhattan since 1889 and provides full service behavioral health care including opioid treatment programs. Patients were identified from those who presented to the ambulatory care center that offers adult, geriatric and dual-diagnosis services. A personalized treatment planning approach was developed in each case and included the time period of the COVID-19 quarantine. <h3>Results</h3> Mr A: 64 year old man with Generalized Anxiety Disorder, Panic Disorder, Opioid Use Disorder in sustained remission on Methadone 270mg daily and Sedative Hypnotic Use Disorder. The patient entered treatment for impending Benzodiazepine withdrawal after losing his provider. He was taking alprazolam 2mg, clonazepam 6m and zolpidem 10mg daily over the past 30 years. Following treatment for acute withdrawal and treatment with a slow taper of clonazepam the patient has been struggling with episodic anxiety and feelings of loss. Isolation and boredom related to COVID-19 quarantine conditions have contributed to this making the issue of worsening anxiety with protracted withdrawal symptoms difficult to delineate. Ms B:74 year old woman with Generalized Anxiety Disorder entered treatment after her provider closed his practice. The patient was prescribed diazepam 40mg, lorazepam 2mg and zolpidem 10mg daily for the past 5 years. In addition she was prescribed dextroamphetamine 20 mg daily for 3 years for fatigue. Over a 2 year period the medications were tapered using clonazepam; the dextroamphetamine was discontinued. While being maintained on clonazepam 0.5mg daily she started to complain of fearfulness, loneliness, insonia and chronic pain which increased with the onset of the COVID-19 quarantine. Mirtazpine 7.5mg was started at bedtime with improvement. Ms D: 59 year old woman with PTSD, Major Depressive Disorder, Alcohol Use Disorder, Cannabis Use Disorder and Cocaine Use Disorder treated with lorazepam 2 mg daily entered treatment after a previous provider was unable to administer Naltrexone LAI. The dose was reduces by 25% every 3 to 4 weeks while mirtazapine was utilized to manage emerging symptoms of depression and insomnia. <h3>Conclusions</h3> We found that patients often entered treatment as a result of prior providers either refusing to continue prescribing benzodiazepines or limiting their practice. Patients responded well to engagement but under the increased stress of COVID-19 quarantine conditions symptoms increasingly emerged. Our population included patients who were also receiving MAT for sustained remission of Opioid Use Disorder and faced greater risks related to benzodiazepine use. Patients were receptive to educational interventions regarding the risks of continuing use and were able to engage in treatment. Despite the proven negative outcomes of chronic use providers continue to prescribe benzodiazepines inappropriately to older adults. The need to care for patients treated with these agents is high. Post-acute withdrawal syndrome is poorly understood and under recognized in older adults. Efforts such as de-prescribing, patient centered approaches to rational prescribing and use remote education programs should be increased. COVID-19 pandemic conditions lead to an increase in overall symptoms reported but did not prevent patients from engaging in successful treatment.

Medicines associated with dependence or withdrawal: a mixed-methods public health review and national database study in England

SummaryBackgroundAntidepressants, opioids for non-cancer pain, gabapentinoids (gabapentin and pregabalin), benzodiazepines, and Z-drugs (zopiclone, zaleplon, and zolpidem) are commonly prescribed medicine classes associated with a risk of dependence or withdrawal. We aimed to review the evidence for these harms and estimate the prevalence of dispensed prescriptions, their geographical distribution, and duration of continuous receipt using all patient-linked prescription data in England.MethodsThis was a mixed-methods public health review, comprising a rapid evidence assessment of articles (Jan 1, 2008, to Oct 3, 2018; with searches of MEDLINE, Embase, and PsycINFO, and the Cochrane and King's Fund libraries), an open call-for-evidence on patient experience and service evaluations, and a retrospective, patient-linked analysis of the National Health Service (NHS) Business Services Authority prescription database (April 1, 2015, to March 30, 2018) for all adults aged 18 years and over. Indirectly (sex and age) standardised rates (ISRs) were computed for all 195 NHS Clinical Commissioning Groups in England, containing 7821 general practices for the geographical analysis. We used publicly available mid-year (June 30) data on the resident adult population and investigated deprivation using the English Indices of Multiple Deprivation (IMD) quintiles (quintile 1 least deprived, quintile 5 most deprived), with each patient assigned to the IMD quintile score of their general practitioner's practice for each year. Statistical modelling (adjusted incident rate ratios [IRRs]) of the number of patients who had a prescription dispensed for each medicine class, and the number of patients in receipt of a prescription for at least 12 months, was done by sex, age group, and IMD quintile.Findings77 articles on the five medicine classes were identified from the literature search and call-for-evidence. 17 randomised placebo-controlled trials (6729 participants) reported antidepressant-associated withdrawal symptoms. Almost all studies were rated of very low, low, or moderate quality. The focus of qualitative and other reports was on patients' experiences of long-term antidepressant use, and typically sudden onset, severe, and protracted withdrawal symptoms when medication was stopped. Between April 1, 2017, and March 31, 2018, 11·53 million individuals (26·3% of residents in England) had a prescription dispensed for at least one medicine class: antidepressants (7·26 million [16·6%]), opioids (5·61 million [12·8%]), gabapentinoids (1·46 million [3·3%]), benzodiazepines (1·35 million [3·1%]), and Z-drugs (0·99 million [2·3%]). For three of these medicine classes, more people had a prescription dispensed in areas of higher deprivation, with adjusted IRRs (referenced to quintile 1) ranging from 1·10 to 1·24 for antidepressants, 1·20 to 1·85 for opioids, and 1·21 to 1·85 for gabapentinoids across quintiles, and higher ISRs generally concentrated in the north and east of England. In contrast, the highest ISRs for benzodiazepines and Z-drugs were generally in the southwest, southeast, and east of England, with low ISRs in the north. Z-drugs were associated with increased deprivation, but only at the highest quintile (adjusted IRR 1·11 [95% CI 1·01–1·22]). For benzodiazepines, prescribing was reduced for people in quintiles 4 (0·90 [0·85–0·96]) and 5 (0·89 [0·82–0·97]). In March, 2018, for each of medicine class, about 50% of patients who had a prescription dispensed had done so continuously for at least 12 months, with the highest ISRs in the north and east. Long-term prescribing was associated with a gradient of increased deprivation.InterpretationIn 1 year over a quarter of the adult population in England had a prescription dispensed for antidepressants, opioids (for non-cancer pain), gabapentinoids, benzodiazepines, or Z-drugs. Long-term (>12 months) prescribing is common, despite being either not recommended by clinical guidelines or of doubtful efficacy in many cases. Enhanced national and local monitoring, better guidance for personalised care, and better doctor–patient decision making are needed.FundingPublic Health England.

Safety and tolerability of sauna detoxification for the protracted withdrawal symptoms of substance abuse

ObjectiveProtracted drug withdrawal symptoms can last months or years after drug cessation, often precipitating a return to substance misuse. We evaluated the safety and preliminary health benefits of a unique chemical exposure regimen based on exercise, sauna and therapeutic nutrients.MethodsThis was a prospective evaluation of 109 individuals sequentially enrolled into a sauna detoxification component of a multi-modal, long-term residential substance abuse treatment centre.ResultsData from medical charts, client self-reports and Short Form Health Survey (SF-36) responses indicated that the Hubbard sauna detoxification method was well tolerated, with a 99% completion rate, including one human immunodeficiency virus and nine hepatitis C positive clients. There were no cases of dehydration, overhydration or heat illness. Statistically significant improvements were seen in both mental and physical SF-36 scores at regimen completion, as well as in Addiction Severity Index and Global Appraisal of Individual Needs Short Screener change scores at rehabilitation program discharge, compared with enrolment.ConclusionsThe regimen lacked serious adverse events, had a very low discontinuation rate and high client-reported satisfaction. The SF-36 data indicated improved physical and emotional symptoms. Therefore, broader investigation of this sauna-based treatment regimen is warranted.

How chronic administration of benzodiazepines leads to unexplained chronic illnesses: A hypothesis

It is thought that an ill defined biochemical cascade may lead to protracted withdrawal symptoms subsequent to discontinuance of routine use of benzodiazepine class drugs and establish chronic illness in some patients. In this review, published findings are presented that support the novel concept that withdrawal from benzodiazepine class drugs can trigger elevated and sustained levels of a potent oxidant called peroxynitrite via potentiation of the L-type voltage-gated calcium channels, and in the later stages of withdrawal, via excessive N-methyl-D-aspartate receptor activity, as well. Potentiation of L-type voltage-gated calcium channels and excessive N-methyl-D-aspartate receptor activity both result in calcium influx into the cell that triggers nitric oxide synthesis. In pathophysiological conditions, such increased nitric oxide synthesis leads to peroxynitrite formation.The downstream effects of peroxynitrite formation that may occur during withdrawal ultimately lead to further peroxynitrite production in a system of overlapping vicious cycles collectively referred to as the NO/ONOO(−) cycle. Once triggered, the elements of the NO/ONOO(−) cycle perpetuate pathophysiology, perhaps including reduced GABAA receptor functioning, that may explain protracted withdrawal associated symptoms while the vicious cycle nature of the NO/ONOO(−) cycle may explain how withdrawal becomes a chronic state.Suboptimal levels of tetrahydrobiopterin may be one risk factor for the development of the protracted withdrawal syndrome as this will lead to partial nitric oxide uncoupling and resultant peroxynitrite formation. Nitric oxide uncoupling results in superoxide production as calcium-dependent nitric oxide synthases attempt to produce nitric oxide in response to L-type voltage-gated calcium channel-mediated calcium influx that is known to occur during withdrawal. The combination of nitric oxide and superoxide produced, as when partial uncoupling occurs, react together in a very rapid, diffusion limited reaction to form peroxynitrite and thereby trigger the NO/ONOO(−) cycle.The NO/ONOO(−) cycle may explain the nature of the protracted withdrawal syndrome and the related constellation of symptoms that are also common in other illnesses characterized as NO/ONOO(−) disorders such as myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia.

SSRI and SNRI withdrawal symptoms reported on an internet forum.

Antidepressant withdrawal symptoms are well-recognised, but their potential duration remains uncertain. We aimed to describe the characteristics of withdrawal associated with two popular classes of antidepressants, including duration. We analysed the content of a sample of posts on an antidepressant withdrawal website. We compared the characteristics of withdrawal associated with SSRIs and SNRIs, including time of onset, duration and nature of symptoms. 110 posts about SSRI withdrawal, and 63 concerning SNRI withdrawal, were analysed. The mean duration of withdrawal symptoms was significantly longer with SSRIs than SNRIs: 90.5 weeks (standard deviation, SD, 150.0) and 50.8 weeks (SD 76.0) respectively; p = 0.043). Neurological symptoms, such as 'brain zaps,' were more common among SNRI users (p = 0.023). Psychosexual/genitourinary symptoms may be more common among SSRI users (p = 0.054). The website aims to help people with antidepressant withdrawal, and is therefore likely to attract people who have difficulties. Length of prior use of antidepressants was long, with a mean of 252.2 weeks (SD 250.8). People accessing antidepressant withdrawal websites report experiencing protracted withdrawal symptoms. There are some differences in the characteristics of withdrawal associated with different classes of antidepressants.

Post–Acute Withdrawal Syndrome, Relapse Prevention, and Homeopathy

Clients coming out of conventional medical detoxification often experience post–acute withdrawal syndrome: symptoms of significant cravings for drugs, as well as mental, emotional, and physical symptoms of protracted withdrawal. These cravings are often the trigger for relapse. This article details a protocol of using Nux vomica, a homeopathic medicine, with three cohorts in two substance abuse treatment settings, with data indicating a positive impact on both immediate symptoms and stabilization in treatment. The immediate benefit is the reduction of frequency and intensity of cravings consistently in all three treatment groups: all participants reported an immediate reduction in cravings. In the first two cohorts, those who chose to use homeopathy completed a six-month substance abuse treatment program at nearly twice the rate of those who did not, and results in the third cohort were also promising. No adverse events were reported. The author concludes that the role of homeopathy for recovery from addiction merits a large-scale formal research study.

Memory retrieval-extinction paradigm and its application on drug addicts

Based on the traditional fear extinction training paradigm, the retrieval-extinction paradigm rewrites fear memory within the reconsolidation window, and reduces their fear response by decreasing the valence of fear stimulus. From the perspective of psychology, the main reason of addicts relapse is that the intensive memory of the painful experience inspired when protracted withdrawal symptoms of drug dependence. The reduction of the sensitivity of drug related memory, which is the key of drug detoxification is to change the memory caused by drug related cues. The retrieval-extinction paradigm provides no drug treatment and a new non-invasive model for addicts, and a new perspective to reduce the relapse rate, and to improve the quality of life of addicts. We can do empirical research which using memory retrieval-estinction paradigm on drug addicts in the future.The memory retrieval paradigm can be applied to empirical research in drug addicts in future. Key words: Relapse; Conditioned reflex; Reconsolidation; Memory retrieval-extinction

Brain-derived neurotrophic factor serum levels in heroin-dependent patients after 26 weeks of withdrawal

BackgroundBrain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of heroin dependence. BDNF expression is dramatically changed during drug withdrawal, and is associated with drug withdrawal syndrome. This study aimed to explore (1) alterations of BDNF serum levels in heroin-dependent patients after long term abstinence; and (2) the association between BDNF serum levels and protracted withdrawal syndrome. MethodFifty-three male heroin-dependent patients and fifty-two gender-matched healthy controls were enrolled in this study. We measured BDNF serum levels at baseline and 26 weeks after heroin abstinence. Moreover, protracted withdrawal symptoms, depression and anxiety symptoms were measured by Protracted Withdrawal Symptoms of Heroin-dependent patients (PWSHA), Self-rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS), respectively. ResultWe found that baseline BDNF serum levels were significantly lower in heroin-dependent patients compared to controls (p<0.01). There was also a significantly difference in BDNF serum levels among heroin-dependent patients at baseline and 26-week follow-up (p<0.01). The BDNF serum levels were not associated with age, BMI, years of education, age of initial use, or duration of use. Of the clinical symptoms measured, the change in BDNF serum levels from baseline to 26-week follow-up was negatively associated with the change in PWSHA scores (r = −0.44, p<0.01, see Table 2 and Figure 2 for details). ConclusionThe results show that the BDNF serum levels in heroin-dependent patients are lower than those of healthy controls at baseline and increased after 26 weeks of abstinence, although the BDNF serum levels are still lower than those of the healthy controls. A negative correlation between the change in BDNF serum levels and protracted withdrawal symptoms was found but needs to be confirmed in further study. The results revealed that BDNF serum level is worth paying attention to in order to further investigate the possibility of it being a biomarker of treatment outcome for opiate dependence.

Animal models of drug relapse and craving: From drug priming-induced reinstatement to incubation of craving after voluntary abstinence.

High rates of relapse to drug use during abstinence is a defining feature of drug addiction. In abstinent drug users, drug relapse is often precipitated by acute exposure to the self-administered drug, drug-associated cues, stress, as well as by short-term and protracted withdrawal symptoms. In this review, we discuss different animal models that have been used to study behavioral and neuropharmacological mechanisms of these relapse-related phenomena. In the first part, we discuss relapse models in which abstinence is achieved through extinction training, including the established reinstatement model, as well as the reacquisition and resurgence models. In the second part, we discuss recent animal models in which drug relapse is assessed after either forced abstinence (e.g., the incubation of drug craving model) or voluntary (self-imposed) abstinence achieved either by introducing adverse consequences to ongoing drug self-administration (e.g., punishment) or by an alternative nondrug reward using a discrete choice (drug vs. palatable food) procedure. We conclude by briefly discussing the potential implications of the recent developments of animal models of drug relapse after voluntary abstinence to the development of medications for relapse prevention.

Nux vomica, the Arnica of Recovery from Addiction: An Exploratory Study of the Use of Homeopathy in the Reduction of Post–Acute Withdrawal Syndrome in Addiction Treatment

Clients coming out of traditional medical detoxification often experience post–acute withdrawal syndrome, symptoms of significant cravings for drugs, as well as mental, emotional and physical symptoms of protracted withdrawal. This article details a protocol of using Nux vomica in three American treatment settings, with data indicating a positive impact on both immediate symptoms and long-term stabilisation in treatment. Consistently in all three groups, those who chose to use homeopathy completed substance abuse treatment programs at a higher rate than those who did not. The authors conclude that the role of homeopathy for recovery from addiction merits further investigation.

Traditional Chinese medicine in treatment of opiate addiction

Traditional Chinese medicine (TCM) includes Chinese medicine and acupuncture. Chinese medicine consists of natural products including plants, animals and minerals. TCM has been practiced in China for more than 2000 years, and for the past 200 years has been used in treatment of drug addiction. Ten Chinese medicines for the treatment of opiate addiction have been approved by the Chinese State Food and Drug Administration (SFDA), and at least 6 are in clinical trials. The general therapeutic principle of Chinese medicine developed was based on its unique theory of " reinforcing healthy Qi and resolving and removing effects of toxicity". Acupuncture, another essential part of TCM, which was developed based on the principle that " functions of the human body are controlled by the ' Jing-Luo' and 'Qi-Xue'system" , has been used not only in China, but also in Europe, the USA and other countries, for controlling opiate addiction. There are some advantages in using TCM for opiate detoxification, including less harmful side effects, high safety and ideal effects in the inhibition of protracted withdrawal symptoms and relapse. Co-administration of TCM with modern medicine shows some synergistic effects in detoxification. Many TCM for detoxification also have efficacy in the rehabilitation of abnormal body functions induced by chronic drug use, including improving immune function, increasing working memory and preventing neurological disorder. Given that TCM is effective in the prevention of relapse and causes fewer side effects, it may be used widely in the treatment of opiate addiction.

Impaired sleep during the post-alcohol withdrawal period in alcoholic patients.

Twenty-seven patients who suffered from alcohol dependence syndrome and who were admitted to the Department of Psychiatry at NCNP were investigated for impaired sleep. The incidence of "insomnia night", when a patient has trouble getting sufficient sleep even after taking additional drugs for insomnia, was used as the index for impaired sleep. "Insomnia night" was observed among 51.9% (14 of 27) of the patients during administration; 18.5% (nine of 27) experienced "insomnia night" only during the withdrawal period. The mean incidence was 3.5 nights of 10 nights for 0-9th day after abstinence and 2.0 nights of 10 nights for 10-19th day after abstinence; 33.3% (nine of 27) claimed "insomnia night" even after the withdrawal period and the highest incidence was the 160-169th day after abstinence, average frequency being 4.4 nights of 10 nights. Impaired sleep emerging after the withdrawal period neared the clinical course of Komiyama's protracted withdrawal symptoms, thus suggesting that it might be one of the protracted withdrawal symptoms.

Excessive Ethanol Drinking Following a History of Dependence: Animal Model of Allostasis

Alcohol withdrawal symptoms, particularly negative emotional states, can persist for months following the removal of alcohol. These protracted withdrawal symptoms have been implicated as an important trigger of relapse to excessive drinking in alcoholics and may represent a long lasting shift in affective tone as a result of chronic alcohol exposure. It was shown previously that ethanol-dependent rats increased their operant responding for ethanol when tested during the first 12 hr after withdrawal. The purpose of the present experiments was to determine the persistence of this finding by examining operant oral ethanol self-administration in rats with a history of physical dependence upon ethanol, detoxified and then allowed a two week period of protracted abstinence. The results of these experiments indicate that operant responding for ethanol was enhanced during protracted abstinence by 30–100% and remained elevated for 4–8 weeks post acute withdrawal. These results have important implications for understanding the characteristics and mechanisms underlying vulnerability to relapse.

Compressed opiate withdrawal syndrome and naltrexone

The oral opiate antagonist naltrexone is in regular use in clinical practice with abstinent opiate-dependent individuals. Acute opioid withdrawal is a well-recognised consequence of consuming naltrexone while opiate dependent. Two cases of naltrexone-induced opiate withdrawal are reported. The compressed nature of the withdrawal syndrome in both of these cases and the implications for the management of protracted withdrawal symptoms are discussed. The theoretical implications of this experimental and clinical phenomenon are reviewed.

Should protracted withdrawal from drugs be included in DSM-IV?

The authors reviewed both clinical data and selected laboratory research related to withdrawal from alcohol, opiates, and stimulants in order to draw a conclusion about whether the phenomenon of protracted withdrawal exists and should be included in DSM-IV. Studies were located through computerized searches and reference sections of published articles. Symptoms extending beyond the period of acute withdrawal in alcohol and opiate dependence have been fairly consistently described; this is not the case with cocaine. Nevertheless, protracted alcohol and opiate withdrawal has not been conclusively demonstrated because of the failure of studies to do multiple time point sampling, to use standardized instruments and control groups, and to re-administer the substance in an attempt to suppress withdrawal symptoms. Further, the concept of protracted withdrawal itself is ambiguously defined. This confounds interpretation of the literature and precludes derivation of a unified concept of the term, which would be necessary for adding the diagnosis to DSM-IV. There is insufficient documentation to justify inclusion of protracted withdrawal in DSM-IV because of methodologic limitations of the studies and lack of consensus definition of the term itself. An outline for conceptualizing protracted withdrawal is offered in which the symptoms can be seen as: 1) a global post-use syndrome, 2) attenuated physiologic rebound, 3) toxic residuals, 4) expression of preexisting symptoms unmasked by cessation of use. Future efforts to identify signs and symptoms of protracted withdrawal should carefully define the parameters of the syndrome.