Abrupt Withdrawal Research Articles

Narcolepsia: o despertar para uma realidade subestimada

Narcolepsy is an underestimated disease that takes about 10 years to be diagnosed. The objective of the present study was to raise the awareness of physicians in general, and psychiatrists in particular, about the importance of considering narcolepsy in their patients in daily clinical practice. The negative impact of narcolepsy on quality of life is significant and comparable to that of epilepsy or schizophrenia. Diagnosis is characterized by the presence of five cardinal symptoms: excessive daytime sleepiness; cataplexy; sleep paralysis; hallucinations; and fragmentation of nocturnal sleep. The multiple sleep latency test is used after a baseline polysomnography to confirm diagnosis. Associated depression, bipolar and anxiety disorders are highlyprevalent in patients with narcolepsy. Patients with narcolepsy are treated with stimulants and low doses of antidepressants. Interestingly, the abrupt withdrawal of antidepressants can cause a transient syndrome similar to cataplexy. Another common finding in patients with narcolepsy is REM sleep behavior disorder after the use of antidepressants. The use of psychostimulants, employed in narcolepsy for excessive daytime sleepiness control, can be accompanied by paranoid psychosis, similar to schizophrenia. The diagnosis, treatment, and management of narcolepsy associated with comorbidities are a challenge and should be given due consideration.

High enhancer, downer, withdrawal helper: Multifunctional nonmedical benzodiazepine use among young adult opioid users in New York City

BackgroundBenzodiazepines are a widely prescribed psychoactive drug; in the U.S., both medical and nonmedical use of benzodiazepines has increased markedly in the past 15 years. Long-term use can lead to tolerance and dependence, and abrupt withdrawal can cause seizures or other life-threatening symptoms. Benzodiazepines are often used nonmedically in conjunction with other drugs, and with opioids in particular—a combination that can increase the risk for fatal and non-fatal overdose. This mixed-methods study examines nonmedical use of benzodiazepines among young adults in New York City and its relationship with opioid use. MethodsFor qualitative analysis, 46 90-minute semi-structured interviews were conducted with young adult opioid users (ages 18–32). Interviews were transcribed and coded for key themes. For quantitative analysis, 464 young adult opioid users (ages 18–29) were recruited using Respondent-Driven Sampling and completed structured interviews. Benzodiazepine use was assessed via a self-report questionnaire that included measures related to nonmedical benzodiazepine and opioid use. ResultsParticipants reported using benzodiazepines nonmedically for a wide variety of reasons, including: to increase the high of other drugs; to lessen withdrawal symptoms; and to come down from other drugs. Benzodiazepines were described as readily available and cheap. There was a high prevalence (93%) of nonmedical benzodiazepine use among nonmedical opioid users, with 57% reporting regular nonmedical use. In bivariate analyses, drug-related risk behaviours such as polysubstance use, drug binging, heroin injection and overdose were strongly associated with regular nonmedical benzodiazepine use. In multivariate analysis, growing up in a middle-income household (earning between $51,000 and $100,000 annually), lifetime overdose experience, having ever used cocaine regularly, having ever been prescribed benzodiazepines, recent drug binging, and encouraging fellow drug users to use benzodiazepines to cope with opioid withdrawal were consistently strong predictors of regular nonmedical benzodiazepine use. ConclusionNonmedical benzodiazepine use may be common among nonmedical opioid users due to its drug-related multi-functionality. Harm reduction messages should account for the multiple functions benzodiazepines serve in a drug-using context, and encourage drug users to tailor their endorsement of benzodiazepines to peers to include safer alternatives.

Intermittent hypoxia training blunts cerebrocortical presenilin 1 overexpression and amyloid-β accumulation in ethanol-withdrawn rats.

Abrupt cessation of chronic alcohol consumption triggers signaling cascades that harm vulnerable brain regions and produce neurobehavioral deficits. We have demonstrated that a program of intermittent, normobaric hypoxia training (IHT) in rats prevents brain damage and neurobehavioral impairment resulting from abrupt ethanol withdrawal (EW). Moreover, EW induced expression of stress-activated protein kinase p38 and presenilin 1 (PS1), the catalytic subunit of γ-secretase that produces the neurotoxic amyloid-β (Aβ) peptides Aβ40 and Aβ42. We tested the hypotheses that 1) IHT limits EW-induced activation of the p38-PS1 axis, thereby attenuating γ-secretase activation and Aβ accumulation, and 2) EW disables heat shock protein 25 (HSP25), a p38 substrate, molecular chaperone, and antioxidant, and provokes protein carbonylation in a manner suppressed by IHT. Adult male rats completed two cycles of a 4-wk ethanol diet (6.5% wt/vol) and a 3-wk EW or an isocaloric, dextrin-based control diet. A 20-day IHT program (5-8 daily cycles of 5-10 min of 9.5-10% fractional inspired O2 + 4 min of 21% fractional inspired O2) was administered during the first EW phase. After the second EW phase, the brain was excised and the prefrontal cortex extracted. PS1, phosphorylated p38 (p-p38), and HSP25 were analyzed by immunoblot, PS1 messenger RNA by quantitative polymerase chain reaction, protein carbonyl content by spectrometry, and Aβ40 and Aβ42 contents by enzyme-linked immunosorbent assay. IHT attenuated the EW-associated increases in PS1, p-p38, Aβ40, Aβ42, and protein carbonyl contents, but not that of PS1 messenger RNA, while preserving functionally competent HSP25 dimers in EW rats. Collectively, these findings suggest that IHT may attenuate EW-induced γ-secretase overactivation by suppressing activation of the p38-PS1 axis and by preventing oxidative protein damage.

Sexual behavioural pattern of orchidectomised and hormone replaced weaner pigs

The persistence or cessation of sexual behaviour after abrupt testosterone withdrawal i.e. castration depends among other things on the age of the animal at castration. The aim of this work is to ascertain the effect of early orchidectomy and subsequent hormone replacement to 24 weeks of age on restoration of sexual behaviour in pigs. Five weeks olds male weaner pigs, 24 in number, randomly grouped into two, twelve in each group were used for this study. The first group was not orchidectomised and not given any form of hormone injection (control). The second group was orchidectomised and given Testosterone enanthate and Oestradiol benzoate hormone replacement respectively (CHR). Orchidectomy was carried out at 5 weeks of age using standard procedure. There was no significant difference in the numbers of subjects mounting in both cases. Whereas only 17% had intromission in the control while 33% had this in the CHR. The control had 0 % ejaculation while 33% ejaculated in the CHR. Sexual behaviour index differs significantly between the two groups with the higher value in the CHR, 2.18±0.10 and 1.56±0.05 in the control. There were no significant difference in the strutting and restless/slashing in the CHR in the control , Violent/biting behaviour was in the control involving all the subjects, 100%, while 83% displayed this in the CHR. Aggressive index is higher in the control than in the CHR, 2.70+0.100 and 2.55+0.05 respectively. The study showed than the CHR (castrated with hormone replacement) group displayed improved sexual behaviour the than control group, although, the latter group was more aggressive.Keywords: Hormonal replacement, Orchidectomy, Weaner pigs, Sexual behaviour

Transient Splenial Lesion Following Abrupt Withdrawal of Carbamazepine.

Transient Splenial Lesion Following Abrupt Withdrawal of Carbamazepine.

Étude rétrospective de l’évaluation et de la prise en charge du syndrome de sevrage brutal en benzodiazépine en milieu hospitalier entre 2000 et 2015

Benzodiazepines are prescribed in many indications and are provider of adverse effects in case of abrupt withdrawal or poorly framed. Withdrawal rules are established by the High Authority for Health. To evaluate the diagnostic and therapeutic modalities of the benzodiazepine withdrawal syndrome, we performed a retrospective single-center study at the University Hospital of Reims, between January 2000 and May 2015, in patients with a withdrawal syndrome following hospital coding. A collection of clinical and laboratory data was performed for each patient, as well as how to obtain the diagnosis, their care and their future. Sixty-eight cases were initially collected, but 16 cases were included. In benzodiazepine withdrawal took place outside the hospital in 68% of cases. The causes were varied: lack of renewal, not issued by the pharmacist, pill errors. Disorders found during the withdrawal symptoms were variable, there were particular digestive, neurological and psychiatric disorders. The use of biological assessments did not provide diagnostic support, however, in 68% of cases a toxicological assay has helped to support. The management of the withdrawal syndrome has been done primarily by reintroducing the same treatment (60%), while in 27% of alprazolam is introduced relay benzodiazepines. It is noted one death possibly linked to the withdrawal syndrome. Despite recommendations and information about the terms of stops, some clinical situations result in withdrawal symptoms, a patient died in our study, death appears in connection with the withdrawal situation. Note that the human factor is the main factor related to the circumstances of occurrence of withdrawal.

Demonstration of rebound phenomenon following abrupt withdrawal of the JAK1 inhibitor oclacitinib

The janus kinase-inhibitor oclacitinib is licensed for the control of pruritus associated with allergic skin diseases in dogs. Strikingly, it has been clinically reported that abrupt withdrawal of oclacitinib leads to a rebound pruritus in dogs. Therefore, the primary objective of this study was to mimic the rebound phenomenon of oclacitinib using a chronic pruritic mouse model of allergic contact dermatitis. Chronic allergic contact dermatitis was induced by repetitive toluene-2,4-diisocyanate (TDI) challenge in BALB/c mice. Oclacitinib was orally administered twice daily at 45mg/kg for 7 days, with concurrent TDI challenge, and then treatment of oclacitinib was abruptly discontinued. Scratching bouts following TDI challenge were evaluated to day 15. Additionally, dorsal root ganglia (DRG) and affected skin were isolated from mice receiving oclacitinib and from mice 24h after oclacitinib withdrawal and were used to determine pruritogen induced Ca2+ signals in sensory neurons, the number of activated dendritic cells (DCs) within DRG, and the cytokine profiles of affected skin. Mice treated with oclacitinib showed a significant decrease in scratching bouts during treatment, then following abrupt withdrawal scratching bouts were significantly increased. Furthermore, following abrupt withdrawal more DRG neurons were activated by pruritogenic cytokines, TNFα positive DCs were significantly increased, and affected skin revealed a significant increase of TNFα and TSLP. In conclusion, while oclacitinib significantly reduced itch during treatment the abrupt withdrawal led to a rapid rebound phenomenon which can be explained by an increase in pruritogenic cytokines and fast peripheral sensitization.

Desmopressin Withdrawal Strategy for Pediatric Enuresis: A Meta-analysis.

A high relapse rate after discontinuation of desmopressin treatment of pediatric enuresis is consistently reported. Structured withdrawal strategies have been used to prevent relapse. To assess the efficacy of a structured withdrawal strategy of desmopressin on the relapse-free rate for desmopressin responder pediatric enuresis. Systematic literature search up to November 2015 on Medline, Embase, Ovid, Science Direct, Google Scholar, Wiley Online Library databases, and related references without language restriction. Related clinical trials were summarized for systematic review. Randomized controlled trials on the efficacy of structured versus abrupt withdrawal of desmopressin in sustaining relapse-free status in pediatric enuresis were included for meta-analysis. Eligible studies were evaluated according to Cochrane Collaboration recommendations. Relapse-free rate was extracted for relative risk (RR) and 95% confidence interval (CI). Effect estimates were pooled via the Mantel-Haenszel method with random effect model. Six hundred one abstracts were reviewed. Four randomized controlled trials (total 500 subjects) of adequate methodological quality were included for meta-analysis. Pooled effect estimates compared with the abrupt withdrawal, structured withdrawal results to a significantly better relapse-free rate (pooled RR: 1.38; 95% CI, 1.17-1.63; P = .0001). Subgroup analysis for a dose-dependent structured withdrawal regimen showed a significantly better relapse-free rate (pooled RR: 1.48; 95% CI, 1.21-1.80; P = .0001). The small number of studies included in meta-analysis represents a major limitation. Structured withdrawal of desmopressin results in better relapse-free rates. Specifically, the dose-dependent structured withdrawal regimen showed significantly better outcomes.

Editorial: Extinction Learning from a Mechanistic and Systems Perspective.

Editorial: Extinction Learning from a Mechanistic and Systems Perspective.

Presumed Pseudotumor Cerebri Syndrome After Withdrawal of Inhaled Glucocorticoids

Pseudotumor cerebri syndrome (PTCS) is characterized by increased intracranial pressure with normal brain parenchyma and cerebrospinal fluid constituents. PTCS after withdrawal of systemic corticosteroids also has been described in children. In contrast, to our knowledge, PTCS after withdrawal of inhaled glucocorticoids has not previously been described. Here we report the case of an 8-year and 6-month-old girl who developed signs and symptoms consistent with PTCS after withdrawal of inhaled glucocorticoids. The patient had excellent adherence to inhaled glucocorticoid therapy for ∼1 year before presentation, after which the therapy was stopped for concern related to poor growth. The withdrawal of inhaled glucocorticoids was associated with the development of severe headaches and diplopia, and further clinical examination led to the patient's diagnosis of likely PTCS. Although its occurrence is likely rare, clinicians caring for the many children receiving inhaled glucocorticoid therapy should be aware of the potential for PTCS after abrupt withdrawal of such treatment, and consider ophthalmology evaluation if patients report suggestive symptoms, such as headaches or vision changes in this context.

Effects of chronic alcohol consumption, withdrawal and nerve growth factor on neuropeptide Y expression and cholinergic innervation of the rat dentate hilus

Several studies have demonstrated the vulnerability of the hippocampal formation (HF) to chronic alcohol consumption and withdrawal. Among the brain systems that appear to be particularly vulnerable to the effects of these conditions are the neuropeptide Y (NPY)-ergic and the cholinergic systems. Because these two systems seem to closely interact in the HF, we sought to study the effects of chronic alcohol consumption (6months) and subsequent withdrawal (2months) on the expression of NPY and on the cholinergic innervation of the rat dentate hilus. As such, we have estimated the areal density and the somatic volume of NPY-immunoreactive neurons, and the density of the cholinergic varicosities. In addition, because alcohol consumption and withdrawal are associated with impaired nerve growth factor (NGF) trophic support and the administration of exogenous NGF alters the effects of those conditions on various cholinergic markers, we have also estimated the same morphological parameters in withdrawn rats infused intracerebroventricularly with NGF. NPY expression increased after withdrawal and returned to control values after NGF treatment. Conversely, the somatic volume of these neurons did not differ among all groups. On other hand, the expression of vesicular acetylcholine transporter (VAChT) was reduced by 24% in ethanol-treated rats and by 46% in withdrawn rats. The administration of NGF to withdrawn rats increased the VAChT expression to values above control levels. These results show that the effects of prolonged alcohol intake and protracted withdrawal on the hilar NPY expression differ from those induced by shorter exposures to ethanol and by abrupt withdrawal. They also suggest that the normalizing effect of NGF on NPY expression might rely on the NGF-induced improvement of cholinergic neurotransmission in the dentate hilus.

A Prospective, Placebo-Controlled Pilot Evaluation of the Effect of Omeprazole on Serum Calcium, Magnesium, Cobalamin, Gastrin Concentrations, and Bone in Cats.

BackgroundChronic proton pump inhibitor administration has been associated with electrolyte and cobalamin deficiency, disrupted bone homeostasis, hypergastrinemia, and rebound acid hypersecretion in humans. It is unknown if this occurs in cats.ObjectivesProlonged oral omeprazole results in altered bone mineral density or content, serum calcium, magnesium, cobalamin, and gastrin concentrations in healthy cats.AnimalsSix healthy adult DSH cats.MethodsIn a within subjects, before and after design, cats received placebo followed by omeprazole (0.83–1.6 mg/kg PO q12h) for 60 days each. Analysis of serum calcium, magnesium, cobalamin, and gastrin concentrations was performed on days 0, 30, and 60. Bone density and content were evaluated on days 0 and 60 of each intervention. Continuous data were analyzed using a two‐way ANOVA (α = 0.006). On day 60 of omeprazole administration, continuous intragastric pH monitoring was performed in 2 cats to evaluate the effects of abrupt withdrawal of omeprazole.ResultsNo significant changes were detected between treatments for any variables, except serum gastrin, which was significantly higher during omeprazole treatment in comparison to placebo (P = 0.002). Evidence of gastric hyperacidity was seen in both cats in which intragastric pH monitoring was performed following cessation of omeprazole.Conclusions and Clinical ImportanceAlthough further studies with larger populations of cats will be needed to draw any definitive conclusions, these preliminary results suggest that prolonged PPI treatment results in hypergastrinemia and abrupt PPI withdrawal might result in RAH in cats.

Algorithm for Canal Gate Operation to Maintain Steady Water Levels Under Abrupt Water Withdrawal

Algorithm for Canal Gate Operation to Maintain Steady Water Levels Under Abrupt Water Withdrawal

Gradual withdrawal of remifentanil infusion may prevent opioid-induced hyperalgesia

BackgroundThe aim of this study was to examine if gradual withdrawal of remifentanil infusion prevented opioid-induced hyperalgesia (OIH) as opposed to abrupt withdrawal. OIH duration was also evaluated. MethodsNineteen volunteers were enrolled in this randomized, double-blinded, placebo-controlled, crossover study. All went through three sessions: abrupt or gradual withdrawal of remifentanil infusion and placebo. Remifentanil was administered at 2.5 ng ml−1 for 30 min before abrupt withdrawal or gradual withdrawal by 0.6 ng ml−1 every five min. Pain was assessed at baseline, during infusion, 45–50 min and 105–110 min after end of infusions using the heat pain test (HPT) and the cold pressor test (CPT). ResultsThe HPT 45 min after infusion indicated OIH development in the abrupt withdrawal session with higher pain scores compared with the gradual withdrawal and placebo sessions (both P<0.01. Marginal mean scores: placebo 2.90; abrupt 3.39; gradual 2.88), but no OIH after gradual withdrawal compared with placebo (P+0.93). In the CPT 50 min after end of infusion there was OIH in both remifentanil sessions compared with placebo (gradual P+0.01, abrupt P<0.01. Marginal mean scores: placebo 4.56; abrupt 5.25; gradual 5.04). There were no differences between the three sessions 105–110 min after infusion. ConclusionsWe found no development of OIH after gradual withdrawal of remifentanil infusion in the HPT. After abrupt withdrawal OIH was present in the HPT. In the CPT there was OIH after both gradual and abrupt withdrawal of infusion. The duration of OIH was less than 105 min for both pain modalities. Clinical trial registrationNCT 01702389. EudraCT number 2011-002734-39.

Inhaled pulmonary vasodilators for persistent pulmonary hypertension of the newborn: safety issues relating to drug administration and delivery devices.

Treatment for persistent pulmonary hypertension of the newborn (PPHN) aims to reduce pulmonary vascular resistance while maintaining systemic vascular resistance. Selective pulmonary vasodilation may be achieved by targeting pulmonary-specific pathways or by delivering vasodilators directly to the lungs. Abrupt withdrawal of a pulmonary vasodilator can cause rebound pulmonary hypertension. Therefore, use of consistent delivery systems that allow for careful monitoring of drug delivery is important. This manuscript reviews published studies of inhaled vasodilators used for treatment of PPHN and provides an overview of safety issues associated with drug delivery and delivery devices as they relate to the risk of rebound pulmonary hypertension. Off-label use of aerosolized prostacyclins and an aerosolized prostaglandin in neonates with PPHN has been reported; however, evidence from large randomized clinical trials is lacking. The amount of a given dose of aerosolized drug that is actually delivered to the lungs is often unknown, and the actual amount of drug deposited in the lungs can be affected by several factors, including patient size, nebulizer used, and placement of the nebulizer within the breathing circuit. Inhaled nitric oxide (iNO) is the only pulmonary vasodilator approved by the US Food and Drug Administration for the treatment of PPHN. The iNO delivery device, INOmax DSIR®IR, is designed to constantly monitor NO, NO2, and O2 deliveries and is equipped with audible and visual alarms to alert providers of abrupt discontinuation and incorrect drug concentration. Other safety features of this device include two independent backup delivery systems, a backup drug cylinder, a battery that provides up to 6 hours of uninterrupted medication delivery, and 27 alarms that monitor delivery, dosage, and system functions. The ability of the drug delivery device to provide safe, consistent dosing is important to consider when selecting a pulmonary vasodilator.

ID 343 – Oral carbamazepine controlled temporal complex partial status epilepticus

Objective Temporal complex partial status epilepticus TCPSE is a condition usually manifest as variable periods of confusion with a prolonged epileptic episode. In our case report on two patients with TCPSE we study the response to carbamazepine after failure of first and second line therapy. Methods Clinical case report. Results Case 1: A 39-year old women with cryptogenic epilepsy, was treated with phenobarbital PB 100 mg/day. Prolonged disturbed consciousness over 3 days, after abrupt withdrawal of PB. Experiencing visual and auditory hallucinations. EEG showed continuous left temporal spike/wave and slow waves discharges. Normal brain MRI. No response to intravenous Diazepam 0.15 mg/kg and PB 15 mg/kg after four days. Clinical improvement and ictal EEG pattern resolved after oral Carbamazepine CBZ treatment 600 mg/day. Case 2: A 61-year old women with symptomatic complex partial seizure disorder, secondary to CNS lymphoma. Was treated with PB 100 mg/day and CBZ600 mg/day. Confusion with agitation and experiencing visual hallucinations, after abrupt withdrawal of CBZ. EEG revealed continuous temporal slow waves. CT scanning was unchanged from imaging studies six month earlier. No response to intravenous Diazepam 0.1 mg/kg and PB 15 mg/day after three days. Improvement in her clinical delirium and EEG pattern after oral CBZ treatment 600 mg/day. Conclusion CBZ was effective and safe in controlling TCPSE in our patients. Oral administration of CBZ is an effective alternative.

Sustained improvements in MRI outcomes with abatacept following the withdrawal of all treatments in patients with early, progressive rheumatoid arthritis

ObjectivesTo assess structural damage progression with subcutaneous abatacept (ABA) in the Assessing Very Early Rheumatoid arthritis Treatment (AVERT) trial following abrupt withdrawal of all rheumatoid arthritis (RA) medication in patients...

Motor Symptoms While Switching Antipsychotics: Should We Taper or Increase The Dose?

Rebound syndromes are well described among several drugs, not only psychotropics. A key element to suspect them is that full manifestations of this phenomenon occur after a given period that depends on the drug´s half-life. Strictly within antipsychotics and their M1 cholinergic receptor blockade, switching from a high- to a low-affinity drug can induce cholinergic rebound, with symptoms like malaise, nausea, vomiting, diarrhea, sialorrhea, extrapyramidal symptoms and akathisia. We know, for example, that abrupt clozapine withdrawal has been associated with cholinergic rebound as well as with serotonin syndrome. PubMed database (last search on 02/15/2016, search terms “cholinergic rebound AND antipsychotics”, with no time limit) shows 27 results for this topic: 04 case reports, 09 review articles, and 02 randomized controlled trials (only one specifically for cholinergic rebound). In the current case, cholinergic symptoms were observed while switching between typical antipsychotics.

Restless Leg Syndrome Induced by an Acute Withdrawal of Oxycodone

Restless leg syndrome (RLS) is a common movement disorder, which disturbs sleep and consequently results in reduced daytime functioning. Alteration in nigral iron deposition and dysfunction of dopaminergic modulation is generally thought to be the main underlying pathophysiology of RLS.1 Oxycodone, a semisynthetic opioid, is one of the treatment options for severe RLS. Its analgesic effect is mediated by k-opioid receptor or μ-opioid receptor which is not clearly identified yet.2 Oxycodone shares many common pharmacological mechanisms with other opioids. There are some reports that abrupt withdrawal of some opioids can induce RLS. Therefore, abrupt withdrawal of oxycodone is expected to induce RLS. However, RLS has never been reported as a withdrawal symptom of oxycodone. We reported a case of secondary RLS, which developed after abrupt withdrawal of oxycodone in a patient with hepatocellular carcinoma associated with severe abdominal pain.

Applying the wisdom of stepping down inhaled corticosteroids in patients with COPD: a proposed algorithm for clinical practice.

Current guidelines for the management of chronic obstructive pulmonary disease (COPD) recommend limiting the use of inhaled corticosteroids (ICS) to patients with more severe disease and/or increased exacerbation risk. However, there are discrepancies between guidelines and real-life practice, as ICS are being overprescribed. In light of the increasing concerns about the clinical benefit and long-term risks associated with ICS use, therapy needs to be carefully weighed on a case-by-case basis, including in patients already on ICS. Several studies sought out to determine the effects of withdrawing ICS in patients with COPD. Early studies have deterred clinicians from reducing ICS in patients with COPD as they reported that an abrupt withdrawal of ICS precipitates exacerbations, and results in a deterioration in lung function and symptoms. However, these studies were fraught with numerous methodological limitations. Recently, two randomized controlled trials and a real-life prospective study revealed that ICS can be safely withdrawn in certain patients. Of these, the WISDOM (Withdrawal of Inhaled Steroids During Optimized Bronchodilator Management) trial was the largest and first to examine stepwise withdrawal of ICS in patients with COPD receiving maintenance therapy of long-acting bronchodilators (ie, tiotropium and salmeterol). Even with therapy being in line with the current guidelines, the findings of the WISDOM trial indicate that not all patients benefit from including ICS in their treatment regimen. Indeed, only certain COPD phenotypes seem to benefit from ICS therapy, and validated markers that predict ICS response are urgently warranted in clinical practice. Furthermore, we are now better equipped with a larger armamentarium of novel and more effective long-acting β2-agonist/long-acting muscarinic antagonist combinations that can be considered by clinicians to optimize bronchodilation and allow for safer ICS withdrawal. In addition to providing a review of the aforementioned, this perspective article proposes an algorithm for the stepwise withdrawal of ICS in real-life clinical practice.