Post-injection Delirium/sedation Syndrome Research Articles

Caveats of mental healthcare act-2017: Recommendation for amendments.

Dear Sir, The rights-based framework in the current Mental Healthcare Act 2017 (MHA-2017) has received a wider acceptance in the minds of policymakers, patients, caregivers, judicial officers, and mental health professionals.[1,2] However, there appears to be a huge gap between acceptance in our minds and implementation at the ground level. Theoretical knowledge of MHA-2017 and the inability to translate it into practice in most of the general hospitals in the country due to systemic issues has created a dilemma in the minds of psychiatry residents. Therefore, it is necessary to have periodic sensitization programs for psychiatry trainees as well as psychiatrists to learn about changing scenarios in mental health legislation in the past five years.[3] The only discipline of Medicine that carries special significance beyond ethical practice involving beneficence, autonomy, non-maleficence, and justice is psychiatry. This practice and the respect for the rights of a person to bring about optimum mental health outcomes have been legally guided. Forensic psychiatry has started to evolve as a subspecialty of psychiatry.[4] However, are psychiatrists in the country confident in dealing with legal issues evolving in the aftermath of MHA-2017 and imparting this practice to postgraduate trainees? Is clinical practice synchronizing with the legal framework? Are we dealing with the paradox of MHA-2017? Are budding psychiatrists across the country in dilemma with regard to MHA-2017? The response of different states is varied in terms of readiness of infrastructure, the constitution of the State Mental Health Authority (SMHA), the functioning of Mental Health Review Boards (MHRB), and overall dismal application of MHA-2017. Are there hasty translations of Western World rules on the infertile grounds of India? More than four years after passing the act, the current level of functional implementation does not appear to be a healthy indicator for the growth of mental health services in the country. This could provoke lawmakers to bring out the amendments to MHA-2017 to best suit the mental health services and practices of the country. In the absence of functional MHRBs, the practical caveats that may require amendments may include providing electroconvulsive therapy (ECT) to children and use of hospital beds for day-care procedures in psychiatry that include but are not limited to the somatic therapies in psychiatry such as administration of electroconvulsive therapy and repetitive transcranial magnetic stimulation (rTMS). It also includes short-term observation for a few hours in a general hospital following administration of long-acting injectables (LAI) antipsychotics and assessment for the appearance of acute side effects such as post-injection delirium sedation syndrome, and acute dystonia and oculogyric crisis. The other concerns requiring immediate attention for the functioning of MHRB include notifying advance directives, continuing admission under special circumstances, and provision of separate wards for children and women under psychiatry in a general hospital. These amendments could also add the role of MHRBs for adolescents involved in juvenile delinquency, child custody, termination of parental rights, and other related issues.[5] The protection of the rights of a person with mental illness should not be viewed as safeguarding oneself from the practice of psychiatry in the absence of full-fledged implementation of MHA-2017. This could be important for making a provision for the psychiatrist witnessing nonsexual or sexual boundary violation to notify the MHRB in advance, a point not placed in MHA-2017. The spirit of the MHA-2017 also does not clarify the role of the Consultation Liaison Psychiatrist and its effective practice in different departments under general hospital units. Further, the role of the psychiatrist in cases requiring cognizance of other specified acts such as the Prevention of Child Sexual Offense (POCSO) Act, Narcotics and Psychoactive Substances (NDPS) Act, The Rights of Persons with Disabilities (RPwD) Act, Right To Information (RTI) Act, etc. should also be viewed in parallel with MHA-2017. Authors emphasize the opportunity of teaching programs to highlight the gaps in training and implementation of MHA-2017.[6] The absence of functional implementation of MHA-2017 requires the churning of thoughts of stakeholders to amend a few provisions such as the formation of the transitional local hospital review board till formal MHRBs are functional.[7] This letter encourages clinicians and researchers to assess the compliance status of Indian states with MHA-2017 and to provide feasible solutions through systematic scientific research. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Post-injection syndrome and olanzapine long-acting injection in patients with schizophrenia: A case series

Pamoate salt of atypical antipsychotic Olanzapine in long-acting injection depot formulation (OLAI) is often used in patients with schizophrenia having poor compliance. This depots formulation having a cluster of adverse events characterized by post-injection delirium/sedation syndrome (PDSS). Here, we present three cases of different age group, different gender suffering from Schizophrenia of varied duration of illness who developed PDSS after receiving OLAI, how they were identified and promptly managed with early intervention. PDSS noted in approximately 0.07% of the injections, in 1.3% of patients. Symptoms such as sedation, delirium, extrapyramidal symptoms, ataxia, autonomic dysfunction, aggression, and speech impairment were reported, onset was immediate to 3–5 h post-injection, patients recovered within 2–72 h. No such risk factors could be identified in any of the cases. PDSS following OLAI occurs when there is accidental intravascular release of high dose of olanzapine. The importance of post-injection syndrome in the above cases lies in the fact that following administration of OLAI a 3–4-h observation period in a health-care facility in the presence of an appropriate qualified personnel is of utmost importance. Furthermore, one should rule out other causes of acute sedation in such patients before establishing the diagnosis of PDSS. There is no specific antidote for olanzapine and almost all such patients improve with conservative and supportive treatment.

Case series profile of olanzapine post-injection delirium/sedation syndrome.

Olanzapine pamoate is an intramuscular depot injection for the treatment of schizophrenia. Approximately 1.4% of patients develop a serious adverse event called post-injection delirium/sedation syndrome (PDSS), characterised by drowsiness, anticholinergic and extrapyramidal symptoms. The objective is to investigate olanzapine PDSS presentations including clinical features and treatment approach. This is a retrospective review of olanzapine PDSS patients from three toxicology units and the NSW Poisons Information Centre between 2017 and 2022. Adult patients were included if they had intramuscular olanzapine then developed PDSS criteria. Clinical symptoms, treatment, timing and length of symptoms were extracted into a preformatted Excel database. There were 18 patients included in the series, with a median age of 49 years (interquartile range [IQR]: 38-58) and male predominance (89%). Median onset time post injection was 30 min (IQR: 11-38). PDSS symptoms predominate with drowsiness, confusion and dysarthria. Median length of symptoms was 24 h (IQR: 20-54). Most common treatment included supportive care without any pharmacological intervention (n = 10), benzodiazepine (n = 4) and benztropine (n = 3). In one case, bromocriptine and physostigmine followed by oral rivastigmine were given to manage antidopaminergic and anticholinergic symptoms respectively. This proposed treatment combination could potentially alleviate some of the symptoms but needs further studies to validate the findings. In conclusion, this case series supports the characterisation of PDSS symptomology predominantly being anticholinergic with similar onset (<1h) and duration (<72 h). Bromocriptine is proposed to manage PDSS if patients develop severe dopamine blockade and physostigmine followed by rivastigmine for anticholinergic delirium.

Safety concerns associated with second-generation antipsychotic long-acting injection treatment. A systematic update.

Background It has been recently suggested that second-generation antipsychotic long-acting injection (SGA-LAIs) are underutilized in clinical practice, despite that their costs significantly impact on national health system budgets. Hence, an updated analysis of safety data shown by SGA-LAIs may contribute to clarify their role in clinical practice. Materials and methods English-language, peer-reviewed articles reporting updated, primary findings on the SGA-LAI safety were identified (updated through an electronic search of five databases - PubMed, EMBASE, PsycInfo, DARE and the Cochrane Library). Results The articles reviewed suggest that the most frequent treatment emergent adverse events (TEAEs) associated with aripiprazole long-acting injection (ARI-LAI) are psychotic symptoms, extrapyramidal symptoms (EPS) and weight gain. Data on olanzapine long-acting injection (OLA-LAI)-associated TEAEs highlight the risk of psychosis, metabolic disturbances and hyperprolactinemia. Four-hundred and forty cases of post-injection delirium/sedation syndrome (PDSS) have also been recorded. Although not reported in reviewed studies, the risk of impulse-control problem and drug reaction with eosinophilia and systemic symptoms (DRESS) ARI- and OLA-associated, respectively, must not be underestimated. With regards paliperidone palmitate 1-month formulation (PP1), the high incidence of clinically relevant weight gain and hyperprolactinemia are both findings of concern. Reviewed data also confirm that the leading cause of death in risperidone long-acting injection (RIS-LAI) clinical trials is suicide. The new 3-month paliperidone palmitate formulation, risperidone sustained release 1-month formulation (RIS-SR1), aripiprazole lauroxil (ARI-LXL) are still lacking exhaustive safety data. Conclusion The risk of specific TEAEs associated with all SGA-LAIs confirms SGA-LAIs do not offer advantages in safety compared with FGA-LAIs or oral antipsychotics and, especially, in early-phase schizophrenia patients. Implementing non pharmacological intervention and strategies can be effective for people with schizophrenia and bipolar disorder who adhere poorly to medication regimens.

Olanzapine pamoate for the treatment of schizophrenia – a safety evaluation

ABSTRACTIntroduction: Non-adherence to long-term treatment is a major issue for patients with schizophrenia and is associated with an increased risk of relapse. Long-acting injectable (LAI) antipsychotics can offer a useful option to improve adherence. Due to the type of sustained-release mechanism, olanzapine pamoate (OLAI) can differ in safety as compared with oral olanzapine. Recent safety data concerning olanzapine pamoate required an update of previous systematic reviews.Areas covered: Safety data were found in US and EU clinical trial registries, and a literature search was undertaken using the databases PubMed and EMBASE to find all relevant published studies. Where appropriate, the number needed to harm and 95% confidence interval for categorical safety outcomes were calculated.Expert opinion: The safety profile of OLAI was similar to the well-known safety profile of oral olanzapine, except for the risk of occurrence of post-injection delirium/sedation syndrome (PDSS). Olanzapine pamoate can be a choice for schizophrenic patients with a history of response to and acceptable tolerance of oral olanzapine, who have easy access to mental healthcare settings with emergency services for the treatment of PDSS. Long-term, prospective studies assessing the efficacy and safety of OLAI and head-to-head comparisons with other LAI and oral antipsychotics are needed.

Rare but Treatment-emergent Extrapyramidal Symptoms-related Adverse Events after Administration of Long-acting Injectable Paliperidone Palmitate

Paliperidone palmitate, the long-acting injectable form of paliperidone (PLAI), is approved for once-monthly intramuscular injection [1]. Several studies suggest that the loading dose regimen for PLAI does not lead to higher rates of extrapyramidal symptoms (EPS)related treatment-emergent adverse events (TEAEs) than the oral formulation [2]. However, reports of post-injection delirium/sedation syndrome (PDSS) by olanzapine LAI raise safety issues of LAI. We report a case, which demonstrates that EPS-related TEAEs can be quite refractory to a number of pharmacological interventions and persist for more than 3 months following PLAI administration.

Baseline characteristics and hospitalizations in patients with schizophrenia receiving olanzapine long-acting injection: an interim analysis from a non-interventional, prospective observational safety study.

BackgroundDepot antipsychotics are a treatment option for medication nonadherence in patients with schizophrenia. Nonadherence can lead to increased relapse and hospitalization rates. This article reports hospitalization data before and after initiation of olanzapine long-acting injection (LAI), a depot antipsychotic.MethodsData were assessed from an ongoing, multinational, prospective, observational post-authorisation safety study being conducted to evaluate post-injection delirium/sedation syndrome (PDSS), an adverse reaction that can occur following injection of olanzapine LAI. Eligible patients were aged ≥18 years, diagnosed with schizophrenia, were prescribed olanzapine LAI, and lived outside the United States. Psychiatric hospitalization and medication data were collected retrospectively for the 6-month period before study entry and prospectively throughout the study. Paired t-tests and McNemar’s tests were used to assess changes in hospitalization incidence and duration. Stepwise Cox proportional hazards models assessed factors associated with hospitalizations. Analyses were based on data from the first 3 years of the continuously enrolling study (N = 668).ResultsThe average duration of olanzapine LAI exposure for all patients was 0.768 years. Of the 529 patients who received at least 1 injection of olanzapine LAI and were not hospitalized at study entry, 8.1 % had at least 1 subsequent psychiatric hospitalization with a mean duration of 2.0 days. Of the 288 patients who had a >6-month follow-up, 8.3 % had at least 1 post-baseline psychiatric hospitalization with a mean duration of 2.3 days. The incidence of hospitalizations in the 6-month period after treatment was significantly lower than that in the 6-month period prior to treatment (8.3 vs 32.6 %, respectively; P < 0.001). Furthermore, mean hospitalization duration decreased from 11.5 days in the 6-month period before treatment to 2.3 days in the 6-month period after treatment (P < 0.001). Psychiatric hospitalization in the prior 12 months (P < 0.0001) and recreational drug use within 24 h of baseline visit (P = 0.015) were identified as potential predictors of time to first psychiatric hospitalization after beginning to take olanzapine LAI. At the time of interim analysis, 5 PDSS events had occurred, which was too few for a full analysis of those events.ConclusionsResults indicate a significant reduction in the incidence and days of hospitalization from the 6-month period before to the 6-month period after olanzapine LAI initiation, which suggests reduced relapse and hospitalization during treatment. Results should be interpreted with caution due to the observational nature of the study and use of retrospective baseline data.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-015-0669-5) contains supplementary material, which is available to authorized users.

A 6-year open-label study of the efficacy and safety of olanzapine long-acting injection in patients with schizophrenia: a post hoc analysis based on the European label recommendation.

PurposeTo assess the long-term efficacy and safety of olanzapine long-acting injection (LAI) in the treatment of schizophrenia, focusing on clinical trial data consistent with the approved indication and dosing recommendations in the European label and which forms the basis for treatment decisions made by clinicians in daily clinical practice.Patients and methodsThis was a post hoc analysis of a 6-year open-label study of olanzapine LAI in patients (male or female, 18–75 years old) with schizophrenia entering this study following feeder studies of olanzapine LAI. Patients were flexibly dosed (45–405 mg, 2- to 4-week intervals), but those receiving oral olanzapine supplementation whose total olanzapine dose was >20 mg/day equivalent were excluded from this post hoc analysis.ResultsData from 669 patients were analyzed (44.5% completed). Positive and Negative Syndrome Scale total scores did not change significantly from baseline to endpoint; Clinical Global Impression-Severity scores improved significantly. Mean weight change was +2.19 kg (P<0.001), with 40.8% of patients experiencing ≥7% weight gain. There were 24 occurrences of post-injection delirium/sedation syndrome (PDSS).ConclusionOlanzapine LAI appeared to be effective in the long-term maintenance of schizophrenia, and the safety profile was consistent with that of oral olanzapine, except for injection-related events and PDSS events.

Olanzapine long-acting injection: a review of first experiences of post-injection delirium/sedation syndrome in routine clinical practice.

BackgroundOlanzapine long-acting injection (LAI) for the treatment of schizophrenia was associated with a cluster of symptoms termed post-injection delirium/sedation syndrome (PDSS) in a small percentage (~2%) of patients during clinical trials. The objective of this analysis was to evaluate the rate and clinical characteristics of PDSS since olanzapine LAI entered commercial use.MethodsCases of PDSS were identified from all reported adverse events during worldwide commercial use of olanzapine LAI through to 1 March 2014. Data sources included two ongoing post-marketing safety studies as well as spontaneously reported adverse events from routine clinical practice over a 5-year period (1 March 2009 to 1 March 2014).ResultsA total of 338 PDSS events were identified. Of these, 91% occurred within 1 hour of injection, and 52% of these occurred within 15 minutes. None of the PDSS events in this analysis were fatal, and most resolved within 72 hours. The most common symptoms (occurring in >30% of cases) were sedation (61%), confusion (56%), dysarthria (54%), somnolence (46%), dizziness (45%) and disorientation (35%). Overall, PDSS occurred with approximately 0.07% of injections and in 0.46–1.03% of patients (reporting and incidence rates from spontaneous reports and post-marketing safety studies, respectively).ConclusionsThe PDSS events reported during routine clinical use of olanzapine LAI are generally similar in incidence and presentation to those reported in clinical trials. Caution should be applied when interpreting spontaneously reported rates of adverse events, however, due to potential under-reporting. Implemented risk-minimisation activities may contribute substantially to the identification and appropriate management of patients with PDSS in clinical practice.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-015-0450-9) contains supplementary material, which is available to authorized users.

“Long-acting” olanzapine in maintenance therapy of schizophrenia: A study with plasma levels

Introduction. This prospective study was performed to evaluate clinical efficacy and tolerability of olanzapine long-acting injection (OLZ-LAI) and the relation between OLZ plasma level (PL) and the clinical outcome in maintenance therapy of schizophrenia. Material and methods. Twenty-five chronic schizophrenic outpatients with age ranging from 18 to 65 years were included in this 9-month study. Patients were given a dosage of either 210 or 300 or 405 mg of OLZ-LAI every 28 days. Patients were evaluated at baseline and every four weeks by Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Symptom Scale (PANSS); at the same time, PL of OLZ was determined. The metabolic profile (aspartate aminotransferase, alanine aminotransferase, high-density lipoprotein, low-density lipoprotein, total cholesterol, and glucose levels) was analyzed every two months. Results. BPRS and total PANSS showed a statistically significant improvement from T2 with a clinical stabilization of psychopathological picture. PL ranged from 4.0 to 78.9 ng/ml (mean 20.59 ng/ml ± 14.66 standard deviation). The coefficient of variation of PLs was related to clinical stabilization. No post-injection delirium sedation syndrome occurred. Conclusions. Our data reveal the efficacy of OLZ-LAI in maintenance treatment of schizophrenia at lower dosages also in comparison with that of oral therapy. OLZ-LAI seems to be useful for guaranteeing constant PL of the drug. A lesser variation of PL was the most predictable factor associated with maintenance of clinical benefit.

Post-injection delirium/sedation syndrome in patients treated with olanzapine pamoate: mechanism, incidence, and management.

Second-generation antipsychotics (SGAs) are a mainstay in the treatment of patients with schizophrenia. However, continuity in intake of the prescribed medication has been one of the greatest challenges in these patients. One option to improve medication adherence is to prescribe depot or long-acting injectable formulations (LAIs) of antipsychotics. Following risperidone, several other SGAs have been introduced as LAIs. Olanzapine pamoate, paliperidone palmitate, and aripiprazole are the new-generation LAIs, which are available for 2- to 4-week intervals of application in many countries. The literature shows a clear advantage of these drugs over placebo regarding symptom reduction and relapse prevention. LAIs show a similar safety profile to oral formulations of the relevant drug, with the exception of olanzapine pamoate, which can lead to rare cases of post-injection delirium/sedation syndrome (PDSS). PDSS is characterized by heavy sedation (possibly including coma) and/or delirium after injection. During PDSS events, patients show higher plasma concentrations of olanzapine, leading to the assumption that unintended partial intravascular injection or blood vessel injury during the injection is causative of PDSS. Therefore, a risk-management plan proposing an observation period of 3h was introduced. In August 2013, a new proposal by the European Medicines Agency terminated the requirement to accompany these patients to their next destination, although this requirement remains in place according to US FDA recommendations.

Within-drug benefit-risk evaluation of olanzapine long-acting injection at one and two years of treatment.

We sought to evaluate the within‐drug benefit‐risk of olanzapine long‐acting injection (LAI) using both quantitative and qualitative methods. Subjects included 1192 adult patients with schizophrenia or schizoaffective disorder who participated in clinical trials with the opportunity for at least two years of continuous treatment with olanzapine LAI (45–405 mg every two to four weeks). Using the Benefit Risk Action Team (BRAT) framework, we evaluated frequency versus duration of benefits and risks commonly observed with atypical antipsychotics. We then used the Transparent Uniform Risk/Benefit Overview (TURBO) method, which weighs the drug's two most medically serious and/or frequent adverse events versus its primary benefit (effectiveness) and an ancillary benefit. The most frequent events among all patients were remaining free of relapse (91.4% for an average of 306 days at one year, 88.4% for 546 days at two years) and symptomatic remission (81.7% for an average of 239 days at one year, 84.1% for 438 days at two years). One‐ and two‐year incidence of ≥7% weight gain was 33.3% and 41.7%. Incidences for sexual dysfunction, hyperprolactinemia, and post‐injection delirium/sedation syndrome (PDSS) were <2%. TURBO ratings unanimously selected PDSS and weight gain as key risks and resulted in an average score in the acceptable benefit‐risk balance range. Copyright © 2014 John Wiley & Sons, Ltd.

Long-Acting Injectable Antipsychotics and the Development of Postinjection Delirium/Sedation Syndrome (PDSS)

Five long-acting injectable (LAI) antipsychotics are currently available in the United States for the treatment of schizophrenia: fluphenazine decanoate, haloperidol decanoate, risperidone microspheres, paliperidone palmitate, and olanzapine pamoate. Additionally, aripiprazole LAI is currently under FDA review. However, research into the safety and tolerability of these LAIs, with particular regard to the development of postinjection delirium/sedation syndrome (PDSS), is limited and has been focused mainly on olanzapine pamoate. This proposal seeks to review data regarding all currently available LAI antipsychotics to determine if a significant association exists between these depot formulations and the development of PDSS. A review of all published literature from 2005 to the present was obtained via a PubMed search for current data regarding the topic of LAIs and the development of PDSS. Keywords used for the search were "long-acting injectable antipsychotics" in association with one of the following: "post-injection delirium/sedation syndrome," "PDSS, " "side effects, " and "tolerability." References to key articles were further explored for relevancy to this proposal. A case analysis based on all 8 olanzapine LAI clinical trials conducted between August 2000 and October 2008 showed an occurrence of PDSS in approximately 0.07% of injections or 1.4% of patients (30 cases in 29 patients). A second case analysis reviewing the clinical trial databases for 15 completed studies and the postmarketing safety database for risperidone LAI versus 10 completed clinical trials of paliperidone palmitate failed to demonstrate an occurrence of PDSS events in patients receiving either LAI treatment. However, one case of PDSS was identified in a placebo group. In 4 randomized, double-blind, placebo-controlled trials, treatment-emergent adverse events leading to treatment discontinuation were similar for paliperidone palmitate and placebo; however, among the most frequently occurring treatment-emergent adverse events was somnolence/sedation (5%-7% paliperidone palmitate group vs 3% placebo). Postinjection delirium/sedation syndrome is a potentially serious adverse event that has been shown to be associated with one currently available LAI antipsychotic, olanzapine pamoate. However, further data are still needed to both support this conclusion and determine if an association exists among other currently available LAIs and PDSS. With the bulk of current evidence coming from registration studies, head-to-head comparison studies between 2 LAIs would help to determine whether the risk of postinjection complications differs among different agents. Further observational studies are also needed to address the incidence, severity, and optimal clinical management of this syndrome.

Olanzapine long-acting injection: insights from an early case series in the UK

Olanzapine long-acting injection depot (OLAI) has been licensed in the UK since 2008. As a result of the recognition during clinical trials that in 0.07% of injections there may be inadvertent intravenous administration leading to post-injection delirium/sedation syndrome (PDSS), the licence mandates a 3 h observation after each injection and accompaniment of the patient to their final destination. The administration of OLAI may thus necessitate organization of local service provisions. We report on how a single healthcare facility in Northern Ireland has treated three initial patients and present a brief case series on these patients and their clinical outcomes. In the first three patients with schizophrenia to receive OLAI, the clinical notes were retrospectively examined to provide clinical data. All three patients had acceptable clinical outcomes showing sustained clinical improvement and have continued on OLAI for over 1 year. Observation has been undertaken within an existing daycare unit staffed by nursing staff and occupational therapists for 3 h after each injection. No issues have emerged from the use of this service that has also provided educational and psycho-educational programmes for the patients. No cases of post-injection delirium/sedation syndrome were reported. There have been no additional cost implications. In patients for whom OLAI may be clinically indicated, the utilization of an existing service to provide the 3 h of observation after each injection may represent a solution with a cost-neutral outcome.

Demystifying Zyprexa Relprevv usage

Zyprexa Relprevv, an extended-release injectable suspension of olanzapine, received FDA approval in December 2009 for the treatment of schizophrenia in adults. Due to the risk of post-injection delirium/sedation syndrome (PDSS) associated with Zyprexa Relprevv usage, the injection is only available through a restricted distribution program. This article reviews the impact of PDSS on the use of Zyprexa Relprevv.

Are the Long-Acting Intramuscular Formulations of Risperidone or Paliperidone Palmitate Associated with Post-Injection Delirium/Sedation Syndrome? An Assessment of Safety Databases

Long-acting injectable (LAI) formulations of antipsychotics are valuable treatment alternatives for patients with psychotic disorders, and understanding their safe use is critical. Post-injection delirium/sedation syndrome (PDSS) has been reported following treatment with one atypical antipsychotic LAI. Clinical databases of risperidone LAI and paliperidone palmitate were explored to identify if cases of PDSS had been observed.No cases of PDSS were identified in 15 completed trials of 3,164 subjects (approximately 115,000 injections) or the postmarketing safety database of risperidone LAI. Only one case of PDSS was identified among 10 completed trials (3,817 subjects, 33,906 injections) of paliperidone palmitate—that case having been reported in a patient randomized to treatment with placebo. Examination of these prospective databases finds no evidence that risperidone LAI and paliperidone palmitate are associated with PDSS and suggest that findings seen with another antipsychotic LAI are not generalizable.

Long-acting atypical injectable antipsychotics in the treatment of schizophrenia: safety and tolerability review

Importance of the field: Although atypical antipsychotics have beneficial efficacy and tolerance, non-adherence and partial adherence remain in patients treated for schizophrenia. Long-acting injectable or depot atypical antipsychotics offer better medication adherence and tolerability advantages. Currently, two drugs are available for the treatment of schizophrenia, risperidone long-acting injectable (RLAI) and olanzapine pamoate (OP).Areas covered in this review: Short- and long-term safety and tolerability data on RLAI and OP from January 2006 through September 2009 were reviewed by performing Medline and PubMed searches, reviewing abstracts and poster presentations, and viewing available material from the FDA and European Medicines Agency.What the reader will gain: RLAI and OP show good short- and long-term safety when treating patients with schizophrenia, with uncommon discontinuation due to adverse effects. RLAI and OP data show rare problems with injection site reactions and patients exposed to injectable treatments prefer to continue injections. Infrequent but serious post-injection delirium sedation syndrome occurred after 1% of OP injections. Weight gain was generally higher among patients treated with OP versus RLAI.Take home message: Healthcare providers, patients and family members should be made aware of the safety and benefits of long-acting injectable atypical antipsychotics in order to diminish the unnecessary restrictions of these therapies for patients with schizophrenia.

Long-acting injectable antipsychotics: focus on olanzapine pamoate.

Medication non-adherence in patients with schizophrenia continues to be a significant problem and threatens successful treatment outcomes. Medication non-adherence is often associated with negative consequences, including symptom exacerbation, more frequent emergency room visits, re-hospitalizations and relapse. Long-acting injectable (LAI) forms of antipsychotics allow for rapid identification of non-adherence, obviate the need for the patient to take the medication on a daily basis and increase adherence to some significant degree. Eli Lilly has developed a long-acting depot formulation of olanzapine, olanzapine pamoate, which has recently been approved by the FDA for the US market, and which will be reviewed here. Olanzapine LAI appears to be an effective antipsychotic at dosages of 210 mg every 2 weeks, 300 mg every 2 weeks and 405 mg every 4 weeks in patients with acute schizophrenia, and at 150 mg every 2 weeks, 300 mg every 2 weeks and at 405 mg every 4 weeks for the maintenance treatment of stable patients. Oral supplementation appears not to be needed, particularly not at the onset of treatment with the LAI as is necessary with risperidone LAI. Its efficacy is in general comparable to the efficacy seen with oral olanzapine at a corresponding dose. The side effect profile is also comparable to the side effects observed with oral olanzapine, including lower rates of extrapyramidal symptoms, prolactin elevation and cardiovascular side effects, but significant metabolic effects. The latter include significant weight gain, lipid abnormalities and glucose dysregulation. While the injection site adverse events are overall mild, the most significant serious adverse event is the post-injection delirium sedation syndrome (PDSS). While rare, this syndrome results from inadvertent intravascular injection of olanzapine LAI and can cause a range of olanzapine overdose-type of symptoms. Olanzapine LAI needs therefore to be administered by trained personnel in settings where a post-injection observation period for at least 3 hours by medical personnel is available. The overall use of olanzapine LAI will probably be limited by the possibility of a PDSS event. Patients who have a history of good response to oral olanzapine and are in need of assured medication administration may present a good indication for its use, provided that the appropriate mental health delivery setting is available.

Patient perspectives in the development and use of long-acting antipsychotics in schizophrenia: focus on olanzapine long-acting injection

Schizophrenia is a chronic mental disorder generally treated with antipsychotic medication. However, non-adherence and partial adherence to antipsychotic medication treatment is common and long-acting injectable "depot" preparations of antipsychotic medications have been used as an alternative to oral medication therapy for patients for whom adherence is a clinically significant problem, as well as for the sake of convenience and in response to patient preference. Olanzapine long-acting injection (OLAI) is a new treatment option and has been approved by several regulatory agencies for the treatment of schizophrenia. OLAI is a crystalline salt formulation of olanzapine and pamoic acid. Efficacy was established in 2 double-blind randomized clinical trials of OLAI for the treatment of acute schizophrenia and for the maintenance of response. The therapeutic OLAI dosages are 150 mg q2 weeks, 210 mg q2 weeks, 300 mg q2 weeks or q4 weeks, and 405 mg q4 weeks, administered by deep intramuscular gluteal injection with a 19-gauge needle. Injection volume ranges from 1 to 2.7 mL. OLAI has essentially the same general tolerability as that of oral olanzapine; however with the depot there is the additional risk of a post-injection delirium sedation syndrome occurring at a rate of 0.07% of injections, requiring a risk management plan that includes observing the patient for 3 hours post injection.

Olanzapine long-acting injection may be associated with post-injection delirium/sedation syndrome (PDSS) if inadvertently administered intravascularly,

Olanzapine long-acting injection may be associated with post-injection delirium/sedation syndrome (PDSS) if inadvertently administered intravascularly,