Antipsychotic Withdrawal Research Articles

Increased antipsychotic drug concentration in hospitalized patients with mental disorders following COVID-19 infection: a call for attention.

Examine the alterations in antipsychotic concentrations following coronavirus disease-2019 (COVID-19) infection among hospitalized patients with mental disorders and conduct an analysis of the factors influencing these changes. Data were collected from inpatients at Beijing Huilongguan Hospital between December 12, 2022, and January 11, 2023, pre- and post-COVID-19. Based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, 329 inpatients with mental disorders were included (3 with incomplete data excluded). Primary outcomes assessed changes in antipsychotic concentrations pre- and post-COVID-19, while secondary outcomes examined factors linked to concentration increases and antipsychotic dose adjustments. Clozapine (P < 0.001), aripiprazole (P < 0.001), quetiapine (P = 0.005), olanzapine (P < 0.001), risperidone (P < 0.001), and paliperidone (P < 0.001) concentrations increased post-COVID-19 in patients with mental disorders. Notably, clozapine concentration surpassing pre-infection levels was highest. Clozapine users were more likely to adjust their dose (50.4%) compared to olanzapine (17.5%) and otherantipsychotics. Moreover, traditional Chinese patent medicines and antibiotics during COVID-19 infection were associated with antipsychotic reduction or withdrawal (OR = 2.06, P = 0.0247; OR = 7.53, P = 0.0024, respectively). Antipsychotic concentrations in hospitalized patients with mental disorders increased after COVID-19 infection, that may be related not only to COVID-19, but also to the use of Chinese patent medicines during infection. The pre-infection concentration and types of antipsychotics, patient's gender, and combination of traditional Chinese medicine or antibiotics, were factors found to correlate with increased drug concentrations and necessitate dose adjustments.

Catatonia in depressive disorder, more usual than it is supposed to be

IntroductionCatatonia is a psychomotor syndrome characterized by various motor, affective and behavioral symptoms. It can occur as a cause of various underlying organic and psychiatric disorders. In Psychiatric nosology is used to specify a subtype of the disorder underlying.Unlike what was assumed in the past, today it is accepted that catatonia is more frequent in affective disorders than in schizophrenia. But despite this, diagnosis and treatment are still late in affective cases on many occasions.Objectives -A case of catatonia is presented to review the diagnostic difficulties that can sometimes entail.-Review treatment algorithm.MethodsWe present the case of a 62-year-old woman, initially diagnosed of major depressive symptoms with psychotic symptoms, showing no response to different treatments, evolving to catatonia, which is diagnosed after screening for neurological and medical diseases.ResultsThe patient had an adequate evolution after the withdrawal of antipsychotics and the application of ECT (Electroconvulsive therapy).Conclusions- It is important to carry out an adequate screening, because many times the symptoms are caused by medical or neurological diseases.-Catatonia has a good prognosis with an early treatment, but it may increase the risk of mortality after 5 days from the onset of symptoms.-It is important to avoid the use of antipsychotics or other dopamine blockers. The use of benzodiazepines and ECT is indicated.Disclosure of InterestNone Declared

Clinical characteristics and outcomes using dexmedetomidine in nonintubated patients: A poison center observational study.

Dexmedetomidine is a central α2 agonist commonly used on intubated patients. It is increasingly being used off-label in nonintubated agitated patients. We sought to determine the overall clinical course, adverse effects, and need for subsequent mechanical ventilation in toxicology patients after treatment with dexmedetomidine. This was a retrospective cohort study conducted by chart review of electronic records from the Virginia Poison Control Center from January 1, 2019 to February 4, 2022. Inclusion criteria consisted of all poison center cases where dexmedetomidine was used. The primary outcome was the presence or absence of clinical improvement following dexmedetomidine use. Secondary outcomes included adverse effects, subsequent intubation, or death. During this study period, there were 220 cases in which dexmedetomidine was used to treat agitation. After exclusions, 70 cases were analyzed. The categories included antimuscarinic (n = 19), polysubstance (n = 16), sedative withdrawal (n = 10), unknown agitation (n = 7), sympathomimetic (n = 5), baclofen withdrawal (n = 3), unknown ingestion (n = 3), sedative/hypnotic (n = 2), antipsychotic (n = 2), hallucinogenic (n = 2), and opioid withdrawal (n = 1). Clinical improvement occurred in 62 of 70 patients (89%). There were no deaths. A total of 4 patients were intubated after starting dexmedetomidine, 2 for refractory agitation and 2 for hypoxia after aspiration. Global clinical improvement was observed in the agitated toxicology patients administered dexmedetomidine. There was one case of intubation secondary to oversedation. Dexmedetomidine could be a useful adjunctive treatment for agitated toxicologic patients but should be studied further before routinely used.

Antipsychotic Abuse, Dependence, and Withdrawal in the Pediatric Population: A Real-World Disproportionality Analysis.

Antipsychotic drugs (APs) aim to treat schizophrenia, bipolar mania, and behavioral symptoms. In child psychiatry, despite limited evidence regarding their efficacy and safety, APs are increasingly subject to off-label use. Studies investigating addictology-related symptoms in young people being scarce, we aimed to characterize the different patterns of AP misuse and withdrawal in children and adolescents relying on the WHO pharmacovigilance database (VigiBase®, Uppsala Monitoring Centre, Sweden). Using the standardized MedDRA Query 'drug abuse, dependence and withdrawal', disproportionality for each AP was assessed with the reporting odds ratio and the information component. A signal was detected when the lower end of the 95% confidence interval of the information component was positive. Results revealed mainly withdrawal symptoms in infants (under 2 years), intentional misuse in children (2 to 11 years), and abuse in adolescents (12 to 17 years). Olanzapine, risperidone, aripiprazole, and quetiapine were disproportionately reported in all age groups, with quetiapine being subject to a specific abuse signal in adolescents. Thus, in adolescents, the evocation of possible recreational consumption may lead to addiction-appropriate care. Further, in young patients with a history of AP treatment, a careful anamnesis may allow one to identify misuse and its role in the case of new-onset symptoms.

“I found hundreds of other people…but I still wasn’t believed” – An exploratory study on lived experiences of antipsychotic withdrawal

ABSTRACT Background Antipsychotic withdrawal refers to a diverse range of symptoms and experiences, which can occur secondary to the cessation or reduction in dose of an antipsychotic drug. This study addresses the shortage of qualitative research that investigates users’ hopes, expectations, and feelings throughout the process, as well as limited research on people prescribed antipsychotics for off-license indications. Methods Nine people recruited from online user-led groups and forums relevant to antipsychotic withdrawal took part in semi-structured interviews via online video. Four of the participants were prescribed antipsychotics for off-licence indications. Reflexive thematic analysis was used to identify themes. Results The themes were: balancing priorities, withdrawal journey, invalidation of experiences and peer community. Findings show the extent of symptoms that can be experienced secondary to antipsychotic discontinuation, they highlight the wider individual context that antipsychotics impact, and the meaningful reasoning behind withdrawal decisions. Discussion This study highlights the importance of developing clinical guidelines for antipsychotic withdrawal to facilitate service-user choice and minimize harms when making decisions about discontinuation. These findings endorse a shift towards full disclosure on the risk of antipsychotic withdrawal effects at the point of starting antipsychotics thus allowing service-users to make informed choices.

Research on maintenance treatment to prevent relapse of psychotic disorders

The issue of antipsychotic (dis)continuation has been a long-standing clinical dilemma. While the routine usage of antipsychotic is associated with side effects and stigma, short-term evidence suggest that the risk of relapse is heightened following antipsychotics withdrawal. Clinical guidelines therefore propose a one to two years duration of maintenance treatment upon remission in first episode psychosis (FEP), but guidance beyond which remains unclear. Only two controlled studies have addressed the long-term consequences of antipsychotic discontinuation. While Wunderink et al. concluded that dose reduction is associated with a higher rate of recovery, Hui et al. found discontinuation to be associated with better clinical outcomes. Data from Hui et al.’s study further suggests that treatment should be maintained for at least the first three years upon remission in FEP in order reduce the risk of relapse, as well as subsequent poor long-term outcome. It is noted that the two studies not only differ in outcome measures, but also in their strategies of “antipsychotic discontinuation”. Considering that discontinuation is a more compelling option to most patients, it may therefore be more clinically relevant. More long-term follow-up discontinuation studies are needed to provide further evidence in the development of treatment guidelines for FEP.

Amisulpride withdrawal akathisia responding to aripiprazole with propranolol in first-onset psychosis: a case report

BackgroundAkathisia tends to develop as an early complication of antipsychotic treatment in a dose-dependent manner. Although withdrawal akathisia has been reported after the discontinuation or dose reduction of typical antipsychotic drugs, akathisia following atypical antipsychotic drug withdrawal remains a rare phenomenon.Case presentationA 24-year-old woman with an acute psychotic episode was admitted and initially treated with aripiprazole. The aripiprazole dose was titrated up to 30 mg/day over 9 days and maintained for the next 3 days; however, her psychotic symptoms persisted without change. She was switched to amisulpride, with the dose increased over 2 weeks to 1000 mg/day. Subsequently, although the patient’s psychotic episode subsided, her serum prolactin levels increased markedly. After discharge, the amisulpride dose was increased to 1200 mg/day owing to auditory hallucinations and was maintained with quetiapine (100–200 mg/day) and benztropine (1 mg/day) for 13 weeks. Given the potential for hyperprolactinemia as a side effect, the amisulpride dose was reduced to 800 mg/day concurrently with the discontinuation of benztropine; however, these changes resulted in severe restlessness without other extrapyramidal symptoms. The withdrawal akathisia disappeared over 2 weeks after switching to aripiprazole (10 mg/day) with propranolol (40 mg/day) and the patient’s prolactin levels had normalized after 6 months of aripiprazole monotherapy.ConclusionsThe present case highlights the potential for the development of withdrawal akathisia when the dose of amisulpride is tapered abruptly. Thus, a slow tapering and careful monitoring are recommended when switching from amisulpride to other antipsychotic drugs. Furthermore, this case suggests that changing the regimen to aripiprazole with propranolol may be a potential option for amisulpride withdrawal akathisia superimposed on pre-existing hyperprolactinemia.

Clinical outcomes following switching antipsychotic treatment due to market withdrawal: a retrospective naturalistic cohort study of pipotiazine palmitate injection (Piportil Depot) discontinuation, subsequent acute care use and effectiveness of medication to which patients switched.

Introduction:Pipotiazine palmitate depot injection (Piportil) was withdrawn from the UK marketplace in 2015. Few studies exist on the clinical impact of such market withdrawal. Purpose: We aimed to identify a cohort of patients switching from pipotiazine following this withdrawal and explore factors associated with effectiveness of the medication switched to and subsequent acute service use.Methods:A naturalistic retrospective cohort study was conducted in Sussex, United Kingdom. Those discontinuing pipotiazine solely due to market withdrawal were identified from electronic patient database and manual searching. Multivariate logistic regression analyses and survival analyses were performed to explore associations between available baseline variables and dichotomous all-cause discontinuation of the next prescribed medication and admission to acute mental health services over the subsequent year.Results:Of 205 patients identified as receiving pipotiazine in October 2014, 137 switched from this due to market withdrawal. Over the subsequent year, 31.5% discontinued the medication to which they were switched and 19% required acute care. Drug class switched to (typical depot vs atypical long acting injection (LAI) vs atypical oral) had no significant association with discontinuation. Switch to atypical LAI was significantly associated with acute care in comparison to typical depot. Those with a schizophrenia diagnosis were significantly less likely to discontinue switched medication or to receive acute care in comparison to those with schizoaffective disorder. Women were significantly more likely to discontinue switched medication than men. Of those requiring acute care, only 38% had required this in the previous 2 years.Conclusions:Antipsychotic market withdrawal has demonstrable negative clinical implications and requires careful clinical management. Increased acute care rates in those receiving an atypical LAI versus a typical depot following pipotiazine suggests lower effectiveness or possible withdrawal effects. No significant difference between depots, LAIs and oral medications on discontinuation supports the importance of a collaborative, fully informed approach when deciding next treatment options.

Antipsychotics for agitation and psychosis in people with Alzheimer's disease and vascular dementia.

Antipsychotics for agitation and psychosis in people with Alzheimer's disease and vascular dementia.

The effect of second-generation antipsychotic withdrawal on the occurrence of vacuous chewing movements in animal models: A review

IntroductionAbrupt discontinuation of antipsychotics is associated with an increased risk of adverse events such as extrapyramidal symptoms in humans. In animal models, vacuous chewing movements may occur after antipsychotic discontinuation. We aim to assess vacuous chewing movements after the discontinuation of second-generation antipsychotics in animal models. MethodsPubMed, EMBASE, and Web of Science databases were searched for studies since inception until January 2, 2021. In addition, we manually searched references from included and relevant studies. Studies were included if a behavioral assessment of vacuous chewing movements (VCMs) in animal models was performed after discontinuation of a second-generation antipsychotic (SGA). Findings will be reviewed qualitatively and discussed with regard to clinical implications. Results5607 studies were screened and five studies were considered eligible for the qualitative analysis. The five studies reported results of behavioral assessments of VCMs after discontinuation of clozapine, olanzapine, and risperidone. VCMs were not reported to be increased after discontinuation of clozapine and olanzapine. However, VCMs were reported to be increased after discontinuation of higher but not lower dosages of risperidone. DiscussionThese findings, based on a limited series of studies, suggest differences in the occurrence of extrapyramidal symptoms between second-generation antipsychotics. More research is needed to determine the magnitude of differences between antipsychotics and implications for clinical practice in humans.

Antipsychotics withdrawal in adults with intellectual disability and challenging behaviour: study protocol for a multicentre double-blind placebo-controlled randomised trial

BackgroundIn people with intellectual disability (ID) and challenging behaviour, antipsychotics (AP) are often used off-label and for a long period. Despite a lack of evidence for efficacy for challenging behaviour and concerns about common and clinically relevant side effects, complete withdrawal often fails. We postulate three possible hypotheses for withdrawal failure: 1. Influence of subjective interpretation of behavioural symptoms by caregivers and family; 2. Beneficial effects from AP treatment on undiagnosed psychiatric illness, through improvement in sleep or a direct effect on behaviour; and 3. Misinterpretation of withdrawal symptoms as a recurrence of challenging behaviour.MethodsTo investigate our hypotheses, we have designed a multicentre double-blind, placebo-controlled randomised trial in which AP (pipamperone or risperidone) are withdrawn. In the withdrawal group, the AP dose is reduced by 25% every 4 weeks and in the control group the dose remains unaltered. Behaviour, sleep, psychiatric disorders, withdrawal symptoms and side effects will be measured and compared between the two groups. If drop-out from the protocol is similar in both groups (non-inferiority), the first hypothesis will be supported. If drop-out is higher in the withdrawal group and an increase is seen in psychiatric disorders, sleep problems and/or behavioural problems compared to the control group, this suggests effectiveness of AP, and indications for AP use should be reconsidered. If drop-out is higher in the withdrawal group and withdrawal symptoms and side effects are more common in the withdrawal group compared to the control group, this supports the hypothesis that withdrawal symptoms contribute to withdrawal failure.DiscussionIn order to develop AP withdrawal guidelines for people with ID, we need to understand why withdrawal of AP is not successful in the majority of people with ID and challenging behaviour. With this study, we will bridge the gap between the lack of available evidence on AP use and withdrawal on the one hand and the international policy drive to reduce prescription of AP in people with ID and challenging behaviour on the other hand.Trial registrationThis trial is registered in the Netherlands Trial Register (NTR 7232) on October 6, 2018 (www.trialregister.nl).

Predictors of Lack of Relapse After Random Discontinuation of Oral and Long-acting Injectable Antipsychotics in Clinically Stabilized Patients with Schizophrenia: A Re-analysis of Individual Participant Data.

To quantify the risk and predictors of relapse among individuals with schizophrenia randomly withdrawn from antipsychotic maintenance treatment. We re-analyzed time-to-event and baseline predictors from placebo arms in five placebo-controlled randomized trials of antipsychotics (n = 688 individuals; 173 stabilized on oral antipsychotic [OAP] and 515 on long-acting injectables [LAI]) for relapse-prevention available in the Yale Open Data Access repository. Using a survival and Cox-proportional hazards regression analyses, we estimated survival rates of "relapse-free" individuals by the end of follow-up (median = 118 days, IQR = 52.0-208.0), the rate of study-confirmed relapse, and adjusted hazard ratios (aHR, 95% confidence intervals [CI]) associated with baseline predictors. We also estimated these parameters for individuals followed for >5 half-lives of the stabilizing antipsychotic, and studied predictors of "rebound psychosis" in OAP-stabilized participants, defined as occurring within 30 days of antipsychotic withdrawal. 29.9% (95%CI = 23.2-38.5) remained relapse-free by the end of follow-up, 11.1% (95%CI = 5.65-21.9) among those OAP-stabilized, 36.4% (95%CI = 28.4-46.7) among those LAI-stabilized. The study-confirmed relapse rate was 45.2%, 62.4% among those OAP-stabilized and 39.4% among those LAI-stabilized. Predictors of relapse included smoking (aHR = 1.54, 95%CI = 1.19-2.00), female sex (aHR = 1.37, 95%CI = 1.08-1.79), and having been stabilized on OAPs vs LAIs (aHR = 3.56, 95%CI = 2.68-4.72). Greater risk of relapse on OAP persisted even after sufficient time had elapsed to clear antipsychotic plasma level among LAI-stabilized (aHR = 5.0, 95%CI = 3.5-7.1). "Rebound psychosis" did not show predictors. Our results corroborate the high relapse risk following antipsychotic withdrawal after symptom stabilization with limited patient-related predictors of safe treatment discontinuation. Stabilization with LAIs reduces the short-/medium-term relapse risk.

Antipsychotic prescribing in dementia

AimsThe majority of people with dementia will develop one or more behavioural or psychological symptoms of dementia (BPSD) as the illness progresses. Treating these symptoms in diverse residential environments is a challenge, with frequent prescribing of antipsychotic medications. The risks and limited benefits of antipsychotic use in this context are well recognised, prompting national guidelines in Ireland to improve prescribing patterns.1) Assess the frequency and appropriateness of prescribing of antipsychotic medication in older adults with BPSD referred to Psychiatry of Old Age service in the West of Ireland (Sligo) by comparing with best practice guidelines.2) Address identified deficits via quality improvement initiatives within department.MethodAudit standards were set using draft National Clinical Guidelines and NICE guidelines for prescribing in dementia to develop a study specific audit tool.Items assessed included: the frequency of review of antipsychotic use, whether or not non-pharmacological methods were trialled, if there was an assessment of benefit of the antipsychotic and discussion or risks, if a reduction/discontinuation of antipsychotic was considered, if metabolic monitoring was achieved.Clinical records for all patients actively under the care of the clinical team with a diagnosis of BPSD were assessed using this tool at the time of the study.Result49 patients with BPSD were attending the service in this time period. 58% (n = 29) of the entire cohort were prescribed an antipsychotic, most commonly quetiapine. Patients cared for at home showed the lowest levels of antipsychotic use at 50% (n = 18), while those who were in nursing home (80%, n = 8) and hospital care (100%, n = 3) showed higher rates, though this sample size was too small to demonstrate statistical significance, χ2 = 5.12 p = 0.077.Exploration of non pharmacological management of BPSD, documentation of discussion of risks of AP medication (metabolic, cardiovascular, falls, sedation, extrapyramidal), attempt at dose reduction or antipsychotic withdrawal were all achieved in less than 45% of cases (range 33–45%).ConclusionThis audit revealed higher than expected rates of antipsychotic prescribing in our BPSD cohort. It also revealed suboptimal documentation around the use of antipsychotics in this population during clinical interactions.A subsequent intervention to the proforma assessment tool to prompt these discussions improved these behaviours, there was no impact on the rates of antipsychotic prescribing.Despite increased attention regarding the limited benefits of antipsychotic medication in BPSD their use remains widespread. Due attention must be given to changing this practice in order to protect this vulnerable patient group.

Service-user efforts to maintain their wellbeing during and after successful withdrawal from antipsychotic medication.

Background:It is well-known that attempting antipsychotic withdrawal can be a fraught process, with a high risk of relapse that often leads people to resume the medication. Nonetheless, there is a group of people who appear to be able to discontinue successfully. Relatively little is known about how people do this.Methods:A convenience sample of adults who had stopped taking antipsychotic medication for more than a year were recruited to participate in semi-structured interviews through an anonymous online survey that investigated antipsychotic medication experiences in New Zealand. Thematic analysis explored participant descriptions of their efforts to maintain their wellbeing during and after the withdrawal process.Results:Of the seven women who volunteered to participate, six reported bipolar disorder diagnoses and one reported diagnoses of obsessive compulsive disorder and depression. The women reported successfully discontinuing antipsychotics for 1.25–25 years; six followed a gradual withdrawal method and had support to prepare for and manage this. Participants defined wellbeing in terms of their ability to manage the impact of any difficulties faced rather than their ability to prevent them entirely, and saw this as something that evolved over time. They described managing the process and maintaining their wellbeing afterwards by ‘understanding myself and my needs’, ‘finding what works for me’ and ‘connecting with support’. Sub-themes expand on the way in which they did this. For example, ‘finding what works for me’ included using a tool-box of strategies to flexibly meet their needs, practicing acceptance, drawing on persistence and curiosity and creating positive life experiences.Conclusion:This is a small, qualitative study and results should be interpreted with caution. This sample shows it is possible for people who experience mania and psychosis to successfully discontinue antipsychotics and safely manage the impact of any symptoms that emerge as a result of the withdrawal process or other life stressors that arise afterwards. Findings suggest internal resources and systemic factors play a role in the outcomes observed among people who attempt to stop taking antipsychotics and a preoccupation with avoiding relapse may be counterproductive to these efforts. Professionals can play a valuable role in facilitating change.

UK psychiatrists' experience of withdrawal of antipsychotics prescribed for challenging behaviours in adults with intellectual disabilities and/or autism.

A high proportion of adults with intellectual disabilities are prescribed off-licence antipsychotics in the absence of a psychiatric illness. The National Health Service in England launched an initiative in 2016, 'Stopping over-medication of people with a learning disability [intellectual disability], autism or both' (STOMP), to address this major public health concern. To gain understanding from UK psychiatrists working with adults with intellectual disabilities on the successes and challenges of withdrawing antipsychotics for challenging behaviours. An online questionnaire was sent to all UK psychiatrists working in the field of intellectual disability (estimated 225). Half of the 88 respondents stated that they started withdrawing antipsychotics over 5 years ago and 52.3% stated that they are less likely to initiate an antipsychotic since the launch of STOMP. However, since then, 46.6% are prescribing other classes of psychotropic medication instead of antipsychotics for challenging behaviours, most frequently the antidepressants. Complete antipsychotic discontinuation in over 50% of patients treated with antipsychotics was achieved by only 4.5% of respondents (n = 4); 11.4% reported deterioration in challenging behaviours in over 50% of patients on withdrawal and the same proportion (11.4%) reported no deterioration. Only 32% of respondents made the diagnosis of psychiatric illness in all their patients themselves. Family and paid carers' concern, lack of multi-agency and multidisciplinary input and unavailability of non-medical psychosocial intervention are key reported factors hampering the withdrawal attempt. There is an urgent need to develop national guidelines to provide a framework for systematic psychotropic drug reviews and withdrawal where possible.

Year in Review: Applying Top Research to the Practice of PALTC Medicine

Year in Review: Applying Top Research to the Practice of PALTC Medicine

Guidance for switching from off-label antipsychotics to pimavanserin for Parkinson's disease psychosis: an expert consensus.

Patients with Parkinson's disease psychosis (PDP) are often treated with an atypical antipsychotic, especially quetiapine or clozapine, but side effects, lack of sufficient efficacy, or both may motivate a switch to pimavanserin, the first medication approved for management of PDP. How best to implement a switch to pimavanserin has not been clear, as there are no controlled trials or case series in the literature to provide guidance. An abrupt switch may interrupt partially effective treatment or potentially trigger rebound effects from antipsychotic withdrawal, whereas cross-taper involves potential drug interactions. A panel of experts drew from published data, their experience treating PDP, lessons from switching antipsychotic drugs in other populations, and the pharmacology of the relevant drugs, to establish consensus recommendations. The panel concluded that patients with PDP can be safely and effectively switched from atypical antipsychotics used off label in PDP to the recently approved pimavanserin by considering each agent's pharmacokinetics and pharmacodynamics, receptor interactions, and the clinical reason for switching (efficacy or adverse events). Final recommendations are that such a switch should aim to maintain adequate 5-HT2A antagonism during the switch, thus providing a stable transition so that efficacy is maintained. Specifically, the consensus recommendation is to add pimavanserin at the full recommended daily dose (34 mg) for 2-6 weeks in most patients before beginning to taper and discontinue quetiapine or clozapine over several days to weeks. Further details are provided for this recommendation, as well as for special clinical circumstances where switching may need to proceed more rapidly.

Clinical Characteristics of Patients With Schizophrenia Who Successfully Discontinued Antipsychotics: A Literature Review.

Although discontinuing antipsychotics clearly increases the risk of relapse in schizophrenia, some patients remain clinically well without continuous antipsychotic treatment. However, data on the characteristics of such patients are still scarce. A systematic literature review was conducted to identify predictive factors for successful antipsychotic discontinuation in schizophrenia using PubMed (last search; June 2018) with the following search terms: (antipsychotic* or neuroleptic) AND (withdraw* or cessat* or terminat* or discontinu*) AND (schizophreni* or psychosis). The search was filtered with humans and English. Factors associated with a lower risk of relapse, when replicated in 2 or more studies with a follow-up period of 3 months or longer, were considered successful. Systematic literature search identified 37 relevant articles. Mean relapse rate after antipsychotic discontinuation was 38.3% (95% confidence interval = 16.0%-60.6%) per year. Factors associated with a lower risk of relapse were being maintained on a lower antipsychotic dose before discontinuation, older age, shorter duration of untreated psychosis, older age at the onset of illness, a lower severity of positive symptoms at baseline, better social functioning, and a lower number of previous relapses. Although this literature review suggests some predictors for successful antipsychotic withdrawal in patients with schizophrenia, the very limited evidence base and unequivocally high relapse rates after discontinuation must remain a matter of serious debate for risk/benefit considerations.

Discontinuation of Long-Term Antipsychotic Drug Use for Behavioral and Psychological Symptoms in Older Adults Aged 65 Years and Older With Dementia

BackgroundAntipsychotic drugs are often used to treat behavioral and psychological symptoms (BPSD) in adults aged 65 years and older with dementia, although there is uncertainty about the effectiveness of long-term use for this indication and there are concerns that they may cause harm. ObjectivesTo evaluate whether discontinuation of long-term antipsychotic drugs for BPSD is successful in adults aged 65 years and older with dementia. This article is based on a Cochrane review updated in 2018. DesignA Cochrane systematic review and meta-analysis. Setting and ParticipantsEight databases were searched in January 2018 to identify 10 randomized controlled trials with 632 older adults. MeasuresWe used standard methodological procedures according to the Cochrane Handbook for Systematic Reviews of Interventions. We assessed the number of patients completing the study. We considered sustained withdrawal of antipsychotics until the end of the study period as successful outcome. ResultsBased on assessment of 7 studies (n = 446), discontinuation may make little or no difference to whether or not participants complete the study (low-quality evidence). In 2 trials, including participants with psychosis, agitation, or aggression who had responded to antipsychotic treatment, discontinuation of antipsychotics was associated with a higher risk of leaving the study prematurely because of symptomatic relapse or a shorter time to symptomatic relapse. We found low-quality evidence from 7 trials (n = 519) that discontinuation may make little or no difference to overall BPSD, measured using various scales. There was some evidence from subgroup analyses in 2 trials that discontinuation may be associated with a worsening of BPSD in participants with more severe BPSD at baseline. ConclusionsOur meta-analysis revealed that there is low-quality evidence that long-term antipsychotic drugs for BPSD may be successfully discontinued in most adults aged 65 and older.

Withdrawal versus continuation of long-term antipsychotic drug use for behavioural and psychological symptoms in older people with dementia.

Antipsychotic agents are often used to treat neuropsychiatric symptoms (NPS) in people with dementia although there is uncertainty about the effectiveness of their long-term use for this indication and concern that they may cause harm, including higher mortality. When behavioural strategies have failed and treatment with antipsychotic drugs is instituted, regular attempts to withdraw them have been recommended in guidelines. Physicians, nurses and families of older people with dementia may be reluctant to stop antipsychotics, fearing deterioration of NPS.This is an update of a Cochrane Review published in 2013. To evaluate whether withdrawal of antipsychotic agents is successful in older people with dementia and NPS in primary care or nursing home settings, to list the different strategies for withdrawal of antipsychotic agents in older participants with dementia and NPS, and to measure the effects of withdrawal of antipsychotic agents on participants' behaviour and assess safety. We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (ALOIS), theCochrane Library, MEDLINE, Embase, PsycINFO, CINAHL, LILACS, clinical trials registries and grey literature sources up to 11 January 2018. We included all randomised, controlled trials comparing an antipsychotic withdrawal strategy to continuation of antipsychotics in people with dementia who had been treated with an antipsychotic drug for at least three months. We used standard methodological procedures according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the quality of evidence for each outcome using the GRADE approach. We included 10 studies involving 632 participants. One new trial (19 participants) was added for this update.One trial was conducted in a community setting, eight in nursing homes and one in both settings. Different types of antipsychotics at varying doses were discontinued in the studies. Both abrupt and gradual withdrawal schedules were used. Reported data were predominantly from studies at low or unclear risk of bias.We included nine trials with 575 randomised participants that used a proxy outcome for overall success of antipsychotic withdrawal. Pooling data was not possible due to heterogeneity of outcome measures used. Based on assessment of seven studies, discontinuation may make little or no difference to whether or not participants complete the study (low-quality evidence).Two trials included only participants with psychosis, agitation or aggression who had responded to antipsychotic treatment. In these two trials, stopping antipsychotics was associated with a higher risk of leaving the study early due to symptomatic relapse or a shorter time to symptomatic relapse.We found low-quality evidence that discontinuation may make little or no difference to overall NPS, measured using various scales (7 trials, 519 participants). There was some evidence from subgroup analyses in two trials that discontinuation may reduce agitation for participants with less severe NPS at baseline, but may be associated with a worsening of NPS in participants with more severe NPS at baseline.None of the studies assessed withdrawal symptoms. Adverse effects of antipsychotics (such as falls) were not systematically assessed. Low-quality evidence showed that discontinuation may have little or no effect on adverse events (5 trials, 381 participants), quality of life (2 trials, 119 participants), or cognitive function (5 trials, 365 participants).There were insufficient data to determine whether discontinuation of antipsychotics has any effect on mortality (very low-quality evidence). There is low-quality evidence that antipsychotics may be successfully discontinued in older people with dementia and NPS who have been taking antipsychotics for at least three months, and that discontinuation may have little or no important effect on behavioural and psychological symptoms. This is consistent with the observation that most behavioural complications of dementia are intermittent and often do not persist for longer than three months. Discontinuation may have little or no effect on overall cognitive function. Discontinuation may make no difference to adverse events and quality of life. Based on the trials in this review, we are uncertain whether discontinuation of antipsychotics leads to a decrease in mortality.People with psychosis, aggression or agitation who responded well to long-term antipsychotic drug use, or those with more severe NPS at baseline, may benefit behaviourally from continuation of antipsychotics. Discontinuation may reduce agitation for people with mild NPS at baseline. However, these conclusions are based on few studies or small subgroups and further evidence of benefits and harms associated with withdrawal of antipsychotic is required in people with dementia and mild and severe NPS.The overall conclusions of the review have not changed since 2013 and the number of available trials remains low.