Akinetic crisis and withdrawal syndromes: guideline "Parkinson's disease" of the German Society of Neurology.

The akinetic crisis is a well-known, rare, potentially life-threatening condition in Parkinson's disease with subacute worsening of akinesia, rigidity, fever, impaired consciousness, accompanying vegetative symptoms and transient dopa-resistance. The akinetic crisis was historically supposed to be a "withdrawal syndrome" in the sense of discontinuation of dopaminergic medication. Recently, other "withdrawal syndromes" as the specific "dopamine agonist withdrawal syndrome" or "deep brain stimulation withdrawal syndrome" have been described as emergency situations with specific subacute symptom constellations. All three conditions require immediate start of the adequate therapy to improve the prognosis. Here, the diagnostic criteria and treatment options of these three acute, severely disabling syndromes will be reported along the current guidelines of the German Parkinson Guideline Group.

[Cannabis use and cannabis use disorders]. / Cannabiskonsum und Cannabiskonsumstörungen.

Cannabis use and cannabis use disorders have taken on a new social significance as a result of partial legalization. In 2021 a total of 4.5 million adults (8.8%) in Germany used the drug. The number of users as well as problematic use have risen in the last decade. Cannabis products with a high delta-9-tetrahydrocannabinol (THC) content and their regular use lead to changes in cannabinoid receptor distribution in the brain and to modifications in the structure and functionality of relevant neuronal networks. The consequences of cannabinoid use are particularly in the psychological functioning and can include intoxication, harmful use, dependence with withdrawal symptoms and cannabis-induced mental disorders. Changes in the diagnostics between ICD-10 and ICD-11 are presented. Interdisciplinary S3 guidelines on cannabis-related disorders are currently being developed and will be finalized shortly.

Selective Serotonin Reuptake Inhibitor and Serotonin-Noradrenaline Reuptake Inhibitor Withdrawal Changes DSM Presentation of Mental Disorders: Results from the Diagnostic Clinical Interview for Drug Withdrawal.

INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) may cause withdrawal at dose decrease, discontinuation, or switch. Current diagnostic methods (e.g., DSM) do not take such phenomenon into account. Using a new nosographic classification of withdrawal syndromes due to SSRI/SNRI decrease or discontinuation [by Psychother Psychosom. 2015;84(2):63-71], we explored whether DSM is adequate to identify DSM disorders when withdrawal occurs. METHODS: Seventy-five self-referred patients with a diagnosis of withdrawal syndrome due to discontinuation of SSRI/SNRI, diagnosed via the Diagnostic Clinical Interview for Drug Withdrawal 1 - New Symptoms of Selective Serotonin Reuptake Inhibitors or Serotonin-Norepinephrine Reuptake Inhibitors (DID-W1), and at least one DSM-5 diagnosis were analyzed. RESULTS: In 58 cases (77.3%), the DSM-5 diagnosis of current mental disorder was not confirmed when the DID-W1 diagnosis of current withdrawal syndrome was established. In 13 cases (17.3%), the DSM-5 diagnosis of past mental disorder was not confirmed when criteria for DID-W1 diagnosis of lifetime withdrawal syndrome were met. In 3 patients (4%), the DSM-5 diagnoses of current and past mental disorders were not confirmed when the DID-W1 diagnoses of current and lifetime withdrawal syndromes were taken into account. The DSM-5 diagnoses most frequently mis-formulated were current panic disorder (50.7%, n = 38) and past major depressive episode (18.7%, n = 14). CONCLUSION: DSM needs to be complemented by clinimetric tools, such as the DID-W1, to detect withdrawal syndromes induced by SSRI/SNRI discontinuation, decrease, or switch, following long-term use.

Impact of an alcohol withdrawal screening and treatment protocol for hospitalized patients.

INTRODUCTION: Alcohol Withdrawal Syndrome (AWS) is a potentially life-threatening complication of alcohol use disorder (AUD) that can be challenging to recognize in hospitalized patients. Our institution implemented universal AUD screening for all patients admitted to a non-critical care venue using the Prediction of Alcohol Withdrawal Severity Scale (PAWSS). At risk patients were then further assessed, utilizing the Glasgow Modified Alcohol Withdrawal Scale (GMAWS), and medicated according to a predetermined protocol. This study sought to determine whether this protocol decreased hospital length of stay, lowered the total benzodiazepine dose administered, and decreased adverse events attributable to AWS. METHODS: This retrospective cohort study was conducted over a 6-year period from 2014 to 2020. The study included patients with an ICD-10 code diagnosis of AWS and subsequently divided them into two groups: pre- and post-protocol introduction. Outcome measures were compared pre- versus post-protocol introduction. RESULTS: There were 181 patient encounters pre- and 265 patient encounters post-protocol. There was no statistically significant difference in median length of stay between the two groups (2.956 days pre and 3.250 days post-protocol, p = 0.058). Post-protocol, there was a statistically significant reduction in median total benzodiazepine dose (13.5 mg and 9 mg lorazepam equivalents pre- and post-protocol, p < 0.001) and in occurrence of delirium tremens (7.7 % pre and 2.3 % post-protocol, p = 0.006). CONCLUSION: Protocol implementation did not reduce length of stay in patients with AUD but was associated with a significant reduction in total benzodiazepine dose and, when adjusted, a non-statistically significant decrease in progression to delirium tremens in hospitalized patients, after applying Bonferroni adjustment.

An acute phase reaction from zoledronate mimicking symptoms seen in opioid withdrawal: a case report.

BACKGROUND: Zoledronate, a bisphosphonate, is a potent first-line treatment for osteoporosis. It is also a preferred treatment for hypercalcemia especially when unresponsive to intravenous fluids. Bisphosphonates can cause acute phase reactions that mimic opioid withdrawal symptoms, which can confound provider decision-making. Our case highlights cognitive bias involving a patient with opioid use disorder who received zoledronate for hypercalcemia secondary to immobilization and significant bone infection. CASE PRESENTATION: A 41-year-old male is admitted with a past medical history of active intravenous opioid use complicated by group A streptococcal bacteremia with L5-S1 discitis and osteomyelitis, L2-L3 osteomyelitis, and left ankle abscess/septic arthritis status post left ankle washout. His pain was well-controlled by acute pain service with ketamine infusion (discontinued earlier), opioids, acetaminophen, buprenorphine-naloxone, cyclobenzaprine, gabapentin, and naproxen. Intravenous opioids were discontinued, slightly decreasing the opioid regimen. A day later, the patient reported tachycardia, diaphoresis, myalgias, and chills, which the primary team reconsulted acute pain service for opioid withdrawal. However, the patient received a zoledronate infusion for hypercalcemia, on the same day intravenous opioids were discontinued. He had no other medications known to cause withdrawal-like symptoms per chart review. Therefore, it was suspected that an acute phase reaction occurred, commonly seen within a few days of bisphosphonate use. CONCLUSION: Zoledronate, well known for causing acute phase reactions, was likely the cause of withdrawal-like symptoms. Acute phase reactions with bisphosphonates mostly occur in the first infusion, and the incidence decreases with subsequent infusions. Symptoms typically occur 24-72 h post-infusion, and last at most for 72 h. Cognitive bias led the primary team to be concerned with opioid withdrawal rather than investigating other causes for the patient's presentation. Therefore, providers should thoroughly investigate potential etiologies and rule them out accordingly to provide the best care. Health care providers should also be aware of the implicit biases that potentially impact the quality of care they provide to patients.

Kratom addiction per DSM-5 SUD criteria, and kratom physical dependence: Insights from dosing amount versus frequency.

BACKGROUND: Kratom products are widely used in the United States, with inadequate understanding of how dosing amounts/frequencies relate to outcomes. METHODS: Between July-November 2022, we enrolled 395 active US adult kratom consumers into a remote study with a baseline survey. We examined self-reported typical dose amounts and frequencies across people and product types, and their associations with outcomes: multiple regression was used to examine whether amounts and frequencies (doses/day) were associated with acute effects, withdrawal symptoms, scores on the Subjective Opioid Withdrawal Scale (SOWS), and addiction (operationalized as DSM-5-based symptoms of kratom-use disorder, KUD). RESULTS: Participants were 54.9% male, aged 38.1 on average, and 81.3% White. Mean length of kratom use was 5.7 years. Most (95.9%) reported regularly using whole-leaf kratom products; 16 (4.1%) reported regular extract use. SOWS scores were mild to moderate on average (13.5, SD 11.9). KUD symptom counts were mostly in the mild/moderate range (80.7%). Withdrawal and KUD symptoms were more closely associated with dose frequency than dose amount. Men reported more acute effects, withdrawal symptoms with cessation, and KUD symptoms than women. CONCLUSIONS: Greater dose amount and frequency were systematically related to the number of withdrawal symptoms upon cessation and to KUD symptoms; the relationship was stronger for dose frequency than amount. Men may have more acute effects and more withdrawal and KUD symptoms than women. Although kratom may be used nonproblematically by some consumers, physical dependence (tolerance, withdrawal, or use to avoid withdrawal) and KUD become more likely with increasing dose frequency.

Study on Risk Factors and Receiver Operator Characteristic Curve of Iatrogenic Withdrawal Syndrome in Pediatric Intensive Care Units: A Retrospective Study.

INTRODUCTION: The aims of this study were to investigate the independent risk factors associated with iatrogenic withdrawal syndrome in pediatric intensive care units (PICUs) and to establish receiver operator characteristic (ROC) curve to facilitate the diagnosis of iatrogenic withdrawal syndrome in clinical settings. METHODS: Pediatric patients who received analgesic and sedative medication at a tertiary hospital in the southern Zhejiang region of China between January 2016 and December 2022 were selected for the study. Clinical case data were retrospectively analyzed to gather information including age, gender, weight, total dose of analgesic and sedative medication, total treatment duration, average maintenance dose, and other relevant parameters. Medically induced withdrawal symptom scores were assessed using the Sophia Observation Scale for Withdrawal Symptoms (SOS). Univariate and multivariate logistic regression analyses were conducted on the above indicators to identify the risk factors for iatrogenic withdrawal, and an ROC curve was constructed. RESULTS: The study encompassed a total of 104 pediatric patients, comprising 47 patients in the SOS score ≥4 group and 57 patients in the SOS score ≤3 group. The incidence of iatrogenic withdrawal was 45.19%. Univariate analysis identified cumulative total dose of fentanyl, average daily dose of fentanyl, average daily dose of midazolam, and patient weight (p < 0.05) as factors associated with iatrogenic withdrawal syndrome. The logistic multiple regression analysis revealed that the average daily dose of fentanyl was an independent risk factor for the occurrence of iatrogenic withdrawal syndrome in critically ill children (p < 0.05). ROC curve analysis indicated an area under the curve of 0.711 (95% CI: 0.610-0.811) with sensitivity and specificity of 73.7% and 61.7%, respectively. CONCLUSION: The average daily maintenance dose of fentanyl holds significant clinical value in diagnosing and evaluating the prognosis of iatrogenic withdrawal syndrome and can provide a scientific foundation for enhancing sedative and analgesic management in clinical practice.

Measuring Objective and Subjective Sleep during Lisdexamfetamine Treatment of Acute Methamphetamine Withdrawal: A Feasibility Study.

INTRODUCTION: Sleep disturbance is common during methamphetamine (MA) use and withdrawal; however, the feasibility of combined subjective-objective measurement of sleep-wake has not been shown in this population. Actigraphy is a well-established, non-invasive measure of sleep-wake cycles with good concordance with polysomnography. This study aimed to investigate the feasibility and utility of using actigraphy and sleep diaries to investigate sleep during MA withdrawal. METHODS: We conducted a feasibility and utility study of actigraphy and sleep diaries during a clinical trial of lisdexamfetamine for MA withdrawal. Participants were inpatients for 7 days, wore an actigraph (Philips Actiwatch 2) and completed a modified Consensus Sleep Diary each morning. Participants were interviewed between days 3-5. RESULTS: Ten participants (mean age 37 years, 90% male) were enrolled. No participant removed the device prematurely. Participants interviewed (n = 8) reported that the actigraph was not difficult or distracting to wear or completion of daily sleep diary onerous. Actigraphic average daily sleep duration over 7 days was 568 min, sleep onset latency 22.4 min, wake after sleep onset (WASO) 75.2 min, and sleep efficiency 83.6%. Sleep diaries underreported daily sleep compared with actigraphy (sleep duration was 56 min (p = 0.008) and WASO 47 min (p < 0.001) less). Overall sleep quality was 4.4 on a nine-point Likert scale within the diary. CONCLUSIONS: Continuous actigraphy is feasible to measure sleep-wake in people withdrawing from MA, with low participant burden. We found important differences in self-reported and actigraphic sleep, which need to be explored in more detail.

Reliability and validity of the Estonian version of the Clinical Institute of Withdrawal Assessment for Alcohol scale.

AIMS: Our aim was to adapt the Clinical Institute of Withdrawal Assessment for Alcohol scale (CIWA-Ar) into Estonian and test its reliability and validity. METHODS: A total of 72 patients with alcohol withdrawal syndrome participated in the study. In order to assess the interrater reliability, at first assessment the CIWA-Ar was simultaneously completed by two nurses. In order to assess the sensitivity of the CIWA-Ar to the changes in the severity of the withdrawal syndrome, as well as its correlations to several indices characterizing the subjects' current condition, the CIWA-Ar, the Clinical Global Impression Severity subscale (CGI-S), the visual analogue scales for the assessment of the general feeling of malaise, anxiety and depression were filled in and the vital signs were measured at inclusion, in 4 h and after the withdrawal syndrome had been resolved. RESULTS: The intraclass correlation coefficient (ICC) for the Estonian version of the CIWA-Ar total score, used as an indicator of interrater reliability, was excellent. The CIWA-Ar had significant correlations with the psychiatrists' CGI-S ratings of the severity of the patient's condition at all assessment points. Significant correlations were also found between CIWA-Ar and patients' self-ratings, the highest correlations found with self-rated anxiety and general feeling of malaise. CIWA-Ar total score did not correlate with simultaneously measured heart rate, systolic and diastolic blood pressure at the first assessment. At the second assessment, heart rate had a significant correlation with the CIWA-Ar total score. CONCLUSION: Our study provides confirmation that the CIWA-Ar tool is well applicable in the Estonian language and culture setting.

The possible clinical utility of the alcohol biomarker phosphatidylethanol for managing suspected alcohol withdrawal in hospitalized patients: A case report.

BACKGROUND AND OBJECTIVES: The decision to initiate pharmacotherapy for alcohol withdrawal is typically based on examining self-reported use of alcohol and symptoms of withdrawal. Phosphatidylethanol (PEth) is a biomarker that could aim in clinical decision-making in withdrawal management. METHODS: This report describes three cases highlighting the potential clinical utility of PEth in caring for individuals at risk for alcohol withdrawal. RESULTS: Two of the cases received phenobarbital when their PEth showed that the risk of withdrawal was low and one case where PEth could have shown this was needed. The results were only available in a delayed fashion, however, could have been useful in informing clinical care. DISCUSSION AND CONCLUSION: PEth can be a useful tool if available without delay. PEth can be used to quickly rule out alcohol withdrawal and avoid misdiagnoses and prolonged hospital stays. SCIENTIFIC SIGNIFICANCE: This is a clinical case study available looking at PEth and withdrawal in hospitalized patients. It proposes that PEth can be used as a way to quickly rule out alcohol withdrawal to avoid misdiagnoses and the possibility of a prolonged hospital stay.

Suicide attempt in a dopamine agonist withdrawal syndrome in Parkinson's disease.

Dopamine agonist withdrawal syndrome (DAWS) results from the reduction or suspension of dopamine agonist medications; it encompasses mainly psychiatric symptoms, including suicidal behaviors. In patients with Parkinson's disease (PD), the impact of DAWS can be significant in terms of distress and disability; however, we must take this syndrome into account as a threatening condition because suicidal behaviors could be developing in the context of DAWS. Here we present a brief case of DAWS affecting a young man with PD, whom abruptly discontinued DA treatment and developed psychiatric symptoms within two weeks which led to a suicidal attempt.

Management of alcohol withdrawal syndrome in patients with alcohol-associated liver disease.

Alcohol-associated liver disease is a common and severe sequela of excessive alcohol use; effective treatment requires attention to both liver disease and underlying alcohol use disorder (AUD). Alcohol withdrawal syndrome (AWS) can be dangerous, is a common barrier to AUD recovery, and may complicate inpatient admissions for liver-related complications. Hepatologists can address these comorbid conditions by learning to accurately stage alcohol-associated liver disease, identify AUD using standardized screening tools (eg, Alcohol Use Disorder Identification Test), and assess risk for and symptoms of AWS. Depending on the severity, alcohol withdrawal often merits admission to a monitored setting, where symptom-triggered administration of benzodiazepines based on standardized scoring protocols is often the most effective approach to management. For patients with severe liver disease, selection of benzodiazepines with less dependence on hepatic metabolism (eg, lorazepam) is advisable. Severe alcohol withdrawal often requires a "front-loaded" approach with higher dosing, as well as intensive monitoring. Distinguishing between alcohol withdrawal delirium and HE is important, though it can be difficult, and can be guided by differentiating clinical characteristics, including time to onset and activity level. There is little data on the use of adjuvant medications, including anticonvulsants, dexmedetomidine, or propofol, in this patient population. Beyond the treatment of AWS, inpatient admission and outpatient hepatology visits offer opportunities to engage in planning for ongoing management of AUD, including initiation of medications for AUD and referral to additional recovery supports. Hepatologists trained to identify AUD, alcohol-associated liver disease, and risk for AWS can proactively address these issues, ensuring that patients' AWS is managed safely and effectively and supporting planning for long-term recovery.

Screening for Alcohol Use Disorder and Management of Alcohol Withdrawal Syndrome in Critical Care Patients.

BACKGROUND: Evidence-based research indicates that subjective questionnaires should be eliminated in screening for alcohol use disorder and management of alcohol withdrawal syndrome in critical care patients. However, transitioning clinicians away from these screening tools remains challenging. OBJECTIVE: To improve screening for alcohol use disorder and management of alcohol withdrawal syndrome in the critical care setting by implementing an evidence-based alcohol use disorder screening tool and alcohol withdrawal syndrome protocol for critical care patients. METHODS: The project site was a 17-bed adult medical intensive care unit in a large, southeastern US teaching hospital. Interventions consisted of the elimination of previously used tools such as the Clinical Institute Withdrawal Assessment for Alcohol-Revised and implementation of the Prediction of Alcohol Withdrawal Severity Scale for alcohol use disorder screening and the Richmond Agitation-Sedation Scale and symptom-triggered benzodiazepine administration for alcohol withdrawal syndrome management. RESULTS: Alcohol use disorder screening among the critical care patient population increased by 49% from before to after the intervention. Of the patients at risk for withdrawal, 79% had an order for monitoring with the new intensive care unit alcohol withdrawal protocol in the postintervention group, compared with 35% who had an order for monitoring with the Clinical Institute Withdrawal Assessment for Alcohol-Revised in the preintervention group. CONCLUSION: The elimination of previously used tools and the implementation of the Prediction of Alcohol Withdrawal Severity Scale and the new intensive care unit alcohol withdrawal protocol improved alcohol use disorder screening and alcohol withdrawal syndrome management among critical care patients.

Acute REM sleep behaviour disorder associated with alcohol withdrawal: A case report and literature review.

INTRODUCTION: Rapid eye movement (REM) sleep behaviour disorder (RBD) is a parasomnia characterised by the loss of REM sleep muscle atonia and the enactment of dreams. Acute RBD associated with alcohol withdrawal syndrome is known, but the studies are limited, particularly on its neurobiological underpinnings and management alongside the withdrawal state. This work attempts to address this using a case study and relevant literature review. CASE PRESENTATION: A 40-year-old male with alcohol dependence (for 20 years) reported new-onset terrifying nightmares and violent behaviours in his sleep precipitated by alcohol withdrawal states for the last 18 months. The polysomnographic finding of REM-without-atonia supported the diagnosis of RBD. He was treated with chlordiazepoxide 100 mg/day (gradually tapered and stopped) and thiamine supplements. Post-discharge, he remained abstinent and symptom-free during the three months of follow-up. DISCUSSION: RBD related to alcohol withdrawal syndrome has been previously described in a few anecdotal reports. Sudden withdrawal from central nervous system suppressants like alcohol is hypothesised to cause a homeostatic imbalance in gamma-aminobutyric acid (GABA) pathways and 'REM rebound', resulting in the clinical and polysomnographic picture of RBD. Benzodiazepines have been found to be useful in both RBD and alcohol withdrawal. CONCLUSIONS: Alcohol withdrawal syndrome may present with acute RBD, which can be treated with a short course of benzodiazepine. However, further studies are needed to explore the long-term course of RBD in these patients.

Dexmedetomidine Withdrawal Syndrome in Children in the PICU: Systematic Review and Meta-Analysis.

OBJECTIVES: To systematically review literature describing the clinical presentation, risk factors, and treatment for dexmedetomidine withdrawal in the PICU (PROSPERO: CRD42022307178). DATA SOURCES: MEDLINE/PubMed, Cochrane, Web of Science, and Scopus databases were searched. STUDY SELECTION: Eligible studies were published from January 2000 to January 2022 and reported clinical data for patients younger than 21 years old following discontinuation of dexmedetomidine after greater than or equal to 24 hours of infusion. DATA EXTRACTION: Abstracts identified during an initial search were screened and data were manually abstracted after full-text review of eligible articles. The Newcastle-Ottawa Scale was used to assess study quality. Summary statistics were provided and Spearman rank correlation coefficient was used to identify relationships between covariates and withdrawal signs. A weighted prevalence for each withdrawal sign was generated using a random-effects model. DATA SYNTHESIS: Twenty-three studies (22 of which were retrospective cohort studies) containing 28 distinct cohorts were included. Median cumulative dexmedetomidine exposure by dose was 105.95 µg/kg (range, 30-232.7 µg/kg), median dexmedetomidine infusion duration was 131.75 hours (range, 20.5-525.6 hr). Weighted estimates for proportion (95% CI) of subjects experiencing withdrawal signs across all cohorts were: hypertension 0.34 (range, 0.0-0.92), tachycardia 0.26 (range, 0.0-0.87), and agitation 0.26 (range, 0.09-0.77). Meta-analysis revealed no correlation between dexmedetomidine exposure variables and withdrawal signs. A moderate negative monotonic relationship existed between the proportion of patients who had undergone cardiac surgery and the proportion experiencing hypertension (correlation coefficient, -0.47; p = 0.048) and tachycardia (correlation coefficient, -0.57; p = 0.008), indicating that in cohorts with a higher proportion of patients who were postcardiac surgery, there were fewer occurrences of hypertension and or tachycardia. CONCLUSIONS: On review of the 2000-2022 literature, dexmedetomidine withdrawal may be characterized by tachycardia, hypertension, or agitation, particularly with higher cumulative doses or prolonged durations. Since most studies included in the review were retrospective, prospective studies are needed to further clarify risk factors, establish diagnostic criteria, and identify optimal management strategies.

A Comparison of Injectable Diazepam and Lorazepam in the Goal-Directed Management of Severe Alcohol Withdrawal.

BACKGROUND: Benzodiazepines are the gold standard for treatment of alcohol withdrawal, yet the selection of a preferred benzodiazepine is limited due to a lack of comparative studies. OBJECTIVES: The primary objective of this study was to compare the efficacy and safety of injectable lorazepam (LZP) and diazepam (DZP) in the treatment of severe alcohol withdrawal syndrome (AWS). METHODS: Retrospective cohort study of adult patients admitted to an intensive care unit with a primary diagnosis of AWS. Subjects who received at least 12 LZP equivalent units (LEU) of injectable DZP or LZP within 24 hours of initiation of the severe AWS protocol were included. The primary outcome was time with Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar) scores at goal over the first 24 hours of treatment. RESULTS: A total of 191 patients were included (DZP n = 89, LZP n = 102). Time with CIWA-Ar scores at goal during the first 24 hours was similar between groups (DZP 12 hours [interquartile range, IQR, = 9-15] vs LZP 14 hours [IQR = 10-17]), P = 0.06). At 24 hours, LEU requirement was similar (DZP 40 [IQR = 22-78] vs LZP 32 [IQR = 18-56], P = 0.05). Drug cost at 24 hours was higher in the DZP group ($204.6 [IQR = 112.53-398.97] vs $8 [IQR = 4.5-14], P < 0.01). CONCLUSION AND RELEVANCE: DZP or LZP are equally efficacious for the treatment of severe AWS. LZP may be preferred due to cost but both medications can be used interchangeably based on availability.