Utilization Of Atypical Antipsychotics Research Articles

PND116 EXAMINE THE SPENDING AND UTILIZATION PATTERNS OF SECOND-GENERATION ANTIPSYCHOTICS BASED ON MEDICAID CLAIMS DATABASE

Antipsychotics have been a major driver of Medicaid prescription drug expenditure, mostly due to high cost and utilization of atypical antipsychotics. The study objective is to describe and evaluate the trends of atypical antipsychotics’ expenditure, utilization and price. A retrospective time-series trend analysis was conducted. The primary data source was the National Medicaid Pharmacy summary claim files collected by the Center for Medicaid/Medicare Services from 1991 to 2017. The quarterly reimbursement amount, number of prescriptions (Rx), reimbursement per prescription and per unit (proxy of drug price) figures were constructed for each branded and generic atypical antipsychotic such as olanzapine, risperidone, quetiapine, aripiprazole, and ziprasidone. The trends were compared between branded and generic drugs in order to assess the impact of generic entry. The annual percentage changes were calculated for reimbursement, utilization, and price.. Total Medicaid spending on atypical antipsychotics increased from $16 million in 1991 to $5.5 billion in 2005, averaged a 59% growth rate. The utilization also increased from 172 thousand Rx to over 21 million Rx in 2005. Post-2006 period saw a sharp decline in both uptake and spending, which bottomed out at $3.6 billion reimbursed and 10.7 million Rx dispensed in 2008, before slowly recovered. Despite the percentage of antipsychotics Rx dispensed as generics exploded from 12% in 2008 to 89% in 2017, the majority of expenditures were driven by branded medications, accounting for over 83%, driven by increased price per Rx. Use of generic drugs grew in marketshare, but low impact on the price of existing branded drugs. Outside of cost, providers and patients’ preferences, off-label usage, FDA warnings and lawsuits are all important factors impacted spending and utilization of this class of drugs.

Musical Hallucinations Treated with Atypical Antipsychotics in a Geriatric Population – A Case Series

Musical hallucinations have been likened to the auditory equivalent of Charles Bonnet Syndrome, which involves complex visual hallucinations, most often in the context of visual impairment. Musical hallucination frequently take the form of hymns, carols, and show-tunes and are strongly associated with hearing loss, with some studies suggesting a prevalence of 2.5–3.6% in the hearing impaired. Musical hallucinations are typically treated with anticonvulsant and anticholinesterase medications, with some studies having evaluated the efficacy of sedative hypnotics, antipsychotics and antidepressants in various psychiatric and medical subpopulations suggesting a heterogeneous spectrum of causes for this disorder. We present two cases of musical hallucinations in both a 70-year-old African American female with past psychiatric history of major depressive disorder who developed hymnal auditory hallucinations during an acute medical and psychiatric admission and an 86-year-old Caucasian female, who complained of hearing gospel music with eventual onset of visual hallucinations after a fall at age 80. Our patients were successfully treated in both the inpatient and outpatient settings with atypical antipsychotics. The presented cases add to the paucity of literature regarding utilization of atypical antipsychotics for treatment of musical hallucinations and demonstrate efficacy to this effect. This study lends further validity to the use of psychopharmacologic agents for novel purposes that have yet to be fully explored.

Unresolved Issues for Utilization of Atypical Antipsychotics in Schizophrenia: Antipsychotic Polypharmacy and Metabolic Syndrome.

Atypical antipsychotics (AAP) are the prevailing form of schizophrenia treatment today due to their low side effects and superior efficacy. Nevertheless, some issues still need to be addressed. First, there are still a large number of patients with treatment-resistant schizophrenia (TRS), which has led to a growing trend to resort to AAP polypharmacy with few side effects. Most clinical treatment guidelines recommend clozapine monotherapy in TRS, but around one third of schizophrenic patients fail to respond to clozapine. For these patients, with clozapine-resistant schizophrenia AAP polypharmacy is a common strategy with a continually growing evidence base. Second, AAP generally have great risks for developing metabolic syndrome, such as weight gain, abnormality in glucose, and lipid metabolism. These metabolic side effects have become huge stumbling blocks in today’s schizophrenia treatment that aims to improve patients’ quality of life as well as symptoms. The exact reasons why this particular syndrome occurs in patients treated with AAP is as yet unclear though factors such as interaction of AAP with neurotransmitter receptors, genetic pholymorphisms, type of AAPs, length of AAP use, and life style of schizophrenic patients that may contribute to its development. The present article aimed to review the evidence underlying these key issues and provide the most reasonable interpretations to expand the overall scope of antipsychotics usage.

Réponse non suffisante : quelle prise en charge ?

Only one third of patients suffering from depression will achieve a satisfactory response with first line treatments and more than half of patients will fail to obtain at least 50 % reduction in their symptoms after 3 months of treatment. This article presents a review of the scientific arguments supporting the various therapeutic strategies when confronted to a first treatment failure after an adequate drug trial. Several pharmacological approaches are possible. A first and classical approach is adjusting the drug dosage (optimization). This strategy is coherent with the pharmacological profile of some antidepressant drugs (tricyclic antidepressants, tetracyclic antidepressants, venlafaxine). There is no scientific basis to a dose-effect relationship with the selective serotonin reuptake inhibitors (SSRIs), as minimal doses of these drugs correspond to a high ratio of serotonin transporter occupation; however increasing doses of SSRIs constitutes a usual practice, endorsed by several experts. A second classic strategy is changing an inefficient antidepressant drug to another antidepressant drug (switch). Theoretically, a different pharmacological class should have more chances to be successful; however, in the case of a failure with an SSRI, an inter-class switch has not consistently proven to be superior to an intra-class switch. In some cases, association of antidepressant drugs can also be an advantageous strategy (combination), particularly in the case of partial response with the first prescribed drug. Due to its particular mechanism of action, mirtazapine is often a drug of choice in the case of such an association. Finally, another approach to recommend in case of partial response is associating an antidepressant drug to another class of drugs, such as lithium, atypical antipsychotics or thyroid hormones (potentiation). Lithium has unfailingly proven its efficacy in case of resistance, but the utilization of atypical antipsychotics, at low-doses, has become increasingly common, certainly, because they are easier to handle. Aside from the pharmacological options, we can consider a number of other strategies, first among them is psychotherapy. Most studies assessing the efficacy of psychotherapy were conducted with this therapy as a first-line treatment. More studies of psychotherapy in depression after unsatisfactory response are distinctly needed. Available data seem to indicate that psychotherapy constitutes an efficient alternative, regardless of the type of psychotherapy (results are more robust in cognitive and behavioural therapies and brief interpersonal psychotherapy, in relation with the greater number of studies using these therapies), with effect sizes comparable to the ones obtained with pharmacological options. Among other strategies, physical exercise has been getting more attention lately, even though evidence in this indication remains deceiving for the moment. Lastly, neuromodulation techniques have an unquestionable place. The rTMS has been largely tested with interesting results. Given the time and staff necessary to conduct this therapy, the question has now switched to how precisely select the patients who will most benefit from rTMs, and how long and at what pace should the sessions take place. ECT is undoubtedly the most efficient treatment, but, apart from life-threatening melancholia and other restricted exceptions, it is usually indicated in multi-resistant depression. Some authors suggest using this therapy earlier, as chronicity of the disease is itself a factor of poor response. Finally, this article reviews also the most recent French and International guidelines in managing patients having showed an unsatisfactory response to a first-line treatment.

Does the use of atypical antipsychotics as adjunctive therapy in depression result in cost savings? Comparing healthcare costs and utilization between second-line treatment options

Background: Several atypical antipsychotics (AAPs) are used as second-line agents for treatment resistant depression. AAPs can be expensive compared to other treatment options and can cause several side effects.Objectives: To estimate healthcare costs and utilization of AAPs compared to other second-line agents.Methods: Observational study using Medicaid claims data (2006–2011). Subjects were depression-diagnosed adult members with at least two prescriptions of antidepressant medications followed by a second-line agent. Gamma generalized linear models (GLM) produced estimates of the difference in mean expenditures among treatment groups after adjusting for individual baseline characteristics using propensity scores. Negative binomial models produced estimates of the difference in number of hospitalizations and emergency department (ED) visits.Results: A total of 3910 members received second-line treatment. Treatment groups were AAPs (n = 2211), augmentation agents other than AAPs (n = 1008), and antidepressant switching (n = 691). AAPs resulted in higher mean adjusted pharmacy costs and higher mean adjusted total mental health-related costs. Mean adjusted total healthcare costs and number of inpatient and ED visits were not different among treatments.Conclusion: The results show no evidence that AAPs used as second-line treatment for depression results in overall cost savings or lower inpatient and ED visits compared to other treatment strategies.

Psychotropic medicine utilization in older people in New Zealand from 2005 to 2013.

Psychotropic medicine utilization has increased worldwide among older people (aged 65 years or older), in relation to utilization of other medicines. The aim of this population-level study was to describe and characterize the national utilization of psychotropic medicines in older people in New Zealand between 2005 and 2013. Repeated cross-sectional analysis of population-level dispensing data was conducted from 1 January 2005 to 31 December 2013. Data on utilization of psychotropic medicines were extracted and categorized in accordance with the World Health Organization Collaborating Centre for Drug Statistics Methodology's Anatomical Therapeutic Chemical classification system. Utilization was measured in terms of the defined daily dose (DDD) per 1,000 older people per day (TOPD). Overall, utilization of psychotropic medicines showed a 22.5 % increase between 2005 and 2013. Utilization increased for antidepressants (from 81.9 to 110.4 DDD/TOPD), antipsychotics (from 6.8 to 8.7 DDD/TOPD) and hypnotics and sedatives (from 59.4 to 65.5 DDD/TOPD); in contrast, utilization of anxiolytics decreased (from 11.4 to 10.7 DDD/TOPD). Utilization of atypical antipsychotics increased (from 4.6 to 6.8 DDD/TOPD), with the highest percentage change in DDD/TOPD being contributed by olanzapine (112.1 %), while utilization of typical antipsychotics declined (from 2.0 to 1.5 DDD/TOPD). Utilization of tetracyclic antidepressants and venlafaxine grew rapidly by 1.5 and 4.5 times, respectively, between 2005 and 2013. Utilization of zopiclone was greater than that of other hypnotics in 2013. Utilization of psychotropic medicines in older people increased by one fifth between 2005 and 2013. Important findings of this study were that: (1) there was a marked increase in utilization of recently funded antidepressants; (2) utilization of atypical antipsychotics increased; (3) there was a move towards utilization of selective serotonin reuptake inhibitors; (4) utilization of zopiclone remained high; and (5) low, standard and high DDD utilization all increased with time.

Cost-Effectiveness of Adjunctive Therapy with Atypical Antipsychotics for Acute Treatment of Major Depressive Disorder

While the clinical utility of atypical antipsychotics has been established in patients with major depressive disorder (MDD) who are refractory to antidepressant therapy, their cost-effectiveness is unknown. To examine the cost-effectiveness of aripiprazole, quetiapine, and olanzapine/fluoxetine in adults with MDD who are refractory to antidepressant therapy. Using techniques of decision analysis, we estimated expected outcomes and costs over 6 weeks in adults with MDD receiving (1) aripiprazole 2-20 mg/day and antidepressant therapy; (2) quetiapine 150 mg/day or 300 mg/day and antidepressant therapy; (3) the fixed-dose combination of olanzapine 6, 12, or 18 mg/day with fluoxetine 50 mg/day; or (4) antidepressant therapy alone. Cost-effectiveness was assessed in terms of the cost per additional responder at 6 weeks, defined as the ratio of the difference in the cost of MDD-related care over 6 weeks versus antidepressant therapy alone to the difference in the number of patients achieving clinical response by 6 weeks. We estimated the model using data from Phase 3 clinical trials of atypical antipsychotics along with other secondary data sources. With antidepressant therapy alone, the estimated clinical response rate at 6 weeks was 30%. Aripiprazole, quetiapine 150 mg/day, quetiapine 300 mg/day, and olanzapine/fluoxetine were estimated to increase clinical response at 6 weeks to 49%, 34%, 38%, and 45%, respectively. Costs of MDD-related care over 6 weeks were estimated to be $192 for antidepressant therapy, $847 for aripiprazole, $541 for quetiapine 150 mg/day, $672 for quetiapine 300 mg/day plus antidepressant therapy, and $791 for olanzapine/fluoxetine. Costs per additional responder (vs antidepressant therapy) over a 6-week period were estimated to be $3447 for aripiprazole, $8725 for quetiapine 150 mg/day, $6000 for quetiapine 300 mg/day, and $3993 for olanzapine/fluoxetine. Atypical antipsychotics substantially increase clinical response at 6 weeks. Cost per additional responder is lower for aripiprazole than for quetiapine or olanzapine/fluoxetine.

Utility of Atypical Antipsychotics in the Treatment of Resistant Unipolar Depression

Many patients fail to achieve an adequate response to antidepressant medication. Growing evidence suggests that atypical antipsychotics may augment antidepressant effects, resulting in a greater potential for response. Atypical antipsychotics possess pharmacological actions that are associated with antidepressant properties, including serotonin 5-HT(2) receptor antagonist and 5-HT(1A) and dopamine receptor partial agonist activity. In fact, the term 'atypical antipsychotic' is an unfortunate remnant of the early indication of these drugs in the treatment of schizophrenia. Soon after their introduction, the usefulness of atypical antipsychotics in bipolar disorder was firmly established and their use in the treatment of mood disorders has far outpaced their use in schizophrenia and other psychotic disorders. Aripiprazole has become the first agent to receive US FDA approval for the adjunctive treatment of unipolar depression. Most recently, Symbyax, a fluoxetine/olanzapine combination, received FDA approval for the acute treatment of treatment-resistant depression. This is the first medication to be FDA approved for this indication. In the present article, the usefulness of antipsychotics in the treatment of resistant unipolar depression is reviewed.

Clinical utilization of atypical antipsychotics in pregnancy and lactation.

To analyze the available literature regarding the safety of atypical antipsychotics in pregnancy and lactation in order to recommend evidence-based strategies for pharmacologic management of psychosis in these conditions. We summarized the results from articles identified via MEDLINE/PubMed/TOXNET (1993-January 31, 2004), using the key terms pregnancy, lactation, breast-feeding, human milk, psychotropic drugs, atypical antipsychotics, olanzapine, quetiapine, risperidone, clozapine, ziprasidone, and aripiprazole. Retrospective studies, clinical observations, and case reports regarding the 6 atypical antipsychotics mentioned above were selected and analyzed. Extensive manual review of pertinent journals and textbooks was also performed. Reviewed studies show that olanzapine and clozapine apparently do not increase the teratogenic risk if administered to pregnant women, while evidence on quetiapine, risperidone, aripiprazole, and ziprasidone is still limited. In contrast, available information is not able to exclude unwanted serious effects associated with the use of all atypical antipsychotics on mother-infant dyads. Furthermore, more than a few studies suggest increased hyperglycemic risk for pregnant women related to atypical antipsychotic therapy during gestation. Finally, published evidence about the effects on long-term infant neurodevelopment of drug exposure through both placenta and breast milk is represented only by sporadic case reports. It is well known that potential consequences of an untreated psychotic episode may be severe and may lead to the mother attempting suicide and/or infanticide. For these reasons, clinicians need to help mothers weigh both fetal and neonatal risks of exposure to drugs against the potential risk they and their infant may incur if the psychiatric illness is not treated. On the other hand, atypical antipsychotics in pregnancy and breast-feeding do not show evident advantages in safety when compared with typical neuroleptic agents. Therefore, we suggest that the most relevant parameters for selecting the best clinical option for pregnant and breast-feeding women with schizophrenia and related disorders remain strongly related to 3 main points: (1). cautious evaluation of the risk/benefit ratio of fetal and neonatal drug exposure, (2). degree of severity of maternal psychiatric illness, and (3). careful preliminary choice of drugs characterized by a balanced safety/efficacy profile.

Trends in antipsychotic use in a Texas medicaid population of children and adolescents: 1996 to 2000.

The purpose of this study was to examine the current trends in prescribing antipsychotics to children and adolescents within the Texas Medicaid Program. Total enrollments of children and adolescents, ranging from infants to 19-year-olds, in the Texas Medicaid Program were determined for each calendar year from 1996 to 2000. Prevalence was defined as the number of children and/or adolescents with at least one Medicaid prescription claim for an antipsychotic per 1,000 enrollees. Trends in prevalence were assessed over a 5-year period using annual descriptive analyses. In addition, total expenditures for antipsychotics were evaluated within this population. Over the 5-year period, an additional 12.25 children and adolescents per 1,000 enrollees (+160%) were prescribed antipsychotics. The prevalence of atypical antipsychotics increased by 13.29 per 1,000 enrollees (+494%) over the same period. In children and adolescents above 2 years of age, the prevalence of antipsychotic use increased in all groups. Antipsychotic usage was more common in children and adolescents between the ages of 10 and 14 years compared to other age groups. Male and female antipsychotic prevalence rates increased during the 5-year period. The increase in total expenditures was related to the increased utilization of atypical antipsychotics.

Pharmacological treatment of psychotic agitation.

The presentation of agitated psychotic patients to psychiatric emergency services is a common occurrence. The traditionally accepted treatment for such patients involves the use of a typical antipsychotic, generally haloperidol. More recently benzodiazepines, such as lorazepam, have been used in combination with antipsychotics due to their sedative properties and relatively benign adverse effect profiles. Standard clinical protocol at many institutions involves the intramuscular administration of 5 to 10mg of haloperidol and 1 to 2mg of lorazepam. Atypical antipsychotics have gained acceptance as first-line treatments for psychotic disorders. These drugs are seen as an improvement over traditional antipsychotics because of their increased efficacy and reduced extrapyramidal effects. The utility of atypical antipsychotics in the emergency setting has been relatively unexplored because slow titration schedules or dose-limiting adverse effects for some members of the class have made this form of treatment impractical. However, the recent availability of oral liquid and rapidly dissolving tablet preparations of some atypical agents has provided useful alternatives in some cases. Nevertheless, for many patients a parenteral drug is the only desirable or feasible treatment option. Intramuscular preparations of the atypical antipsychotics olanzapine and ziprasidone have been developed, and are close to launch in the US. The availability of a rapid-acting intramuscular preparation of an atypical antipsychotic could represent a significant advancement in the treatment of agitation associated with psychosis.

PMH35: PATTERNS OF ANTIDEPRESSANT AND ANTIPSYCHOTIC MEDICATION USE IN MEDICAID, 1995-1999

OBJECTIVES: This study sought to: 1) analyze trends in utilization of antidepressant and antipsychotic medications in Medicaid between 1995 and 1999; 2) gauge the utilization and diffusion of new generation, branded antidepressants and antipsychotics during this period. METHODS: The study was based on a time-series analysis of quarterly, state-level, Medicaid pharmaceutical claims, as administered by HCFA. Data from 45 states were suitable for analysis. RESULTS: In 1998, antidepressants and antipsychotics accounted for 9% of Medicaid prescriptions, but 19% of expenditures. From 1995 to 1998, Medicaid prescriptions for antidepressant and antipsychotic medications grew by 40% and 20%, respectively; corresponding expenditures grew by 96% and 160%. The growth rate in both prescriptions and expenditures for antidepressants and antipsychotics outpaces that observed in Medicaid pharmacy benefits as a whole by more than two-fold. In 1995, new generation antidepressants and antipsychotics accounted for 44% and 17.5% of all prescriptions for Medicaid antidepressants and antipsychotics, respectively. By 1998, these new generation drugs had accounted for 62% and 51% of all Medicaid prescriptions for antidepressants and antipsychotics. CONCLUSIONS: Antidepressants and antipsychotics account for a large proportion of Medicaid pharmaceutical prescriptions and reimbursements. The total Medicaid market for antidepressants and antipsychotics grew dramatically over this four-year period. The impact of newer antidepressants and antipsychotics on expenditures is disproportionate to the number of prescriptions for these agents. New generation antidepressants and antipsychotics have been accepted into common use within Medicaid programs. Increased Medicaid expenditures for antidepressants have been driven both by the uptake of new generation agents and by increased overall prescription volume. Increased Medicaid expenditures for antipsychotics have been driven by increased utilization of atypical antipsychotics. Utilization of new-generation antidepressants and antipsychotics varies among the states; not all states have adopted new generation agents as quickly as others.