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Case AB is a 32-year-old male with a 12-year history of schizophrenia who is effectively treated but has the following residual symptoms: disorganized thinking, auditory hallucinations, flattened affect, decreased speech productivity, and amotivation. Additionally, the patient complains of having a poor memory, slow processing speed, and occasional difficulty interpreting social situations. His most recent Abnormal Involuntary Movement Scale (AIMS) score, which is used to assess patients for tardive dyskinesia, was 0, and he meets 3 of 5 criteria for metabolic syndrome (increased waist circumference, decreased serum high-density lipoprotein cholesterol, increased serum triglycerides). AB was recently discharged from a hospitalization related to an exacerbation of psychosis. His discharge medications were: paliperidone 12 mg by mouth once daily, benztropine 0.5 mg by mouth twice daily, clonazepam 0.5 mg by mouth 3 times daily, and divalproex 500 mg by mouth 3 times daily. The patient aspires to become employed once again and is a new participant in an intensive outpatient program (IOP) that assists individuals with schizophrenia with maintaining symptom control, strengthening cognition, and becoming job ready.

INTRODUCTION

Schizophrenia is an illness with a complex pathophysiology that affects an individual's perceptions, thoughts, behaviors, and cognition.^1-3 This illness has been thought to be associated with excessive dopamine activity in the limbic area of the brain. This is, in turn, connected to a patient's experience of positive symptoms, which include auditory hallucinations, paranoid delusions, and disorganized thinking. Accordingly, antipsychotic medications used to treat this illness act to reduce the activation of dopamine D2 receptors. Schizophrenia, however, is symptomatically much more than positive symptoms related to excessive limbic dopamine. Schizophrenia may also be associated with changes in the activities of several other neurotransmitters, including serotonin (5- HT), gamma-aminobutyric acid, and glutamate.^1,3

People with schizophrenia may have both negative symptoms and cognitive deficits occurring simultaneously with positive symptoms.^2,3 Negative symptoms, which may result from too little dopamine activity in the prefrontal cortex, include lack of motivation, flattened affect, and decreased speech productivity. Cognitive deficits may also be related to reduced prefrontal dopamine activity and are represented in schizophrenia by decreased concentration, memory, and processing speed. Individuals with schizophrenia may also have poor social cognition, which relates to how they process, store, and apply information about other people and about social situations.⁴

Antipsychotic medications possess a pharmacology that antagonizes the D2 receptor and results in reduced severity of positive symptoms. This activity is believed to be a key treatment effect related to the improvement of symptoms of acute exacerbations of psychosis (i.e., a condition in which an individual experiences a loss of contact with reality; in schizophrenia, this typically means a worsening of auditory hallucinations, paranoia, and delusional thinking). Antipsychotics, however, have variable efficacy for treating symptoms of schizophrenia. In many clinical trials, antipsychotic responders are defined as patients who achieve at least a 30% reduction in their total rating scale scores. For example, Macek et al⁵ defined clinical response to TAK-063 (an inhibitor of phosphodiesterase being investigated for antipsychotic efficacy in schizophrenia) as at least a 30% decrease from baseline in a participant's total Positive and Negative Syndrome Scale (PANSS) score. (PANSS is a 30-item rating scale used to measure symptom severity.) Such treatment goals for schizophrenia contrast those for other mental health conditions: for example, for individuals who are diagnosed with major depression and are treated with an antidepressant, symptomatic remission, not simply a reduction in symptoms, is the treatment goal.⁶

Treatment-adherent patients with schizophrenia who achieve improvement in symptoms will typically have reduced severity of positive symptoms, but they will experience very little, if any, improvement in negative symptoms and cognitive deficits related to their illness. Minimally improved negative symptoms and cognitive deficits, which often account for most of a patient's residual symptoms, can be major obstacles for patients in their efforts to regain higher levels of function, illness recovery, and social reintegration.⁷

Case, continued AB has had a long, episodic history of treatment non-adherence with oral antipsychotic medications. Prior to his recent hospitalization, he had been effectively treated with olanzapine. Four weeks before being hospitalized, he began taking his olanzapine much less consistently because of "side effects." Two weeks before hospitalization, his auditory hallucinations told him that olanzapine was "poison," so he stopped taking it completely. Over the next 2 weeks, AB experienced a worsening of his positive symptoms that ultimately led him to begin accusing strangers of breaking in to his apartment and stealing his clothes. He was subsequently brought to the emergency department at the local city hospital.

TREATMENT NON-ADHERENCE IN SCHIZOPHRENIA

Antipsychotic treatment non-adherence is a leading contributor to an individual's risk for relapse of schizophrenia. Substantial rates of non-adherence to oral antipsychotic treatment have been documented for many years.^8-25 While complete (i.e., 100%) adherence to a prescribed treatment is preferred, this level is not routinely achieved by most individuals. From both research and real-world perspectives, antipsychotic treatment adherence is considered to be "good" when an individual is taking his or her medication at least 70% to 80% of the time.²⁶

Rates of non-adherence

Different methods have been used to evaluate treatment non-adherence in schizophrenia, but, overall, non-adherence rates have ranged between 2.3% and 58.4%, with many investigators reporting rates greater than 25%.²⁶ A commonly cited study about antipsychotic treatment discontinuation is the Clinical Antipsychotic Trials of Intervention Effectiveness, or CATIE,²⁷ which was a large, federally funded clinical study that had the primary objective of investigating time to antipsychotic treatment discontinuation for any reason. Study participants were randomized to receive 1 of 5 antipsychotics: risperidone (Risperdal) 1.5 to 6 mg/day, olanzapine (Zyprexa) 7.5 to 30 mg/day, perphenazine (Trilafon) 8 to 32 mg/day, ziprasidone (Geodon) 40 to 160 mg/day, or quetiapine (Seroquel) 200 to 800 mg/day. The rates of treatment non-adherence differed among the antipsychotics (range, 64%-82%), but, by the end of 18 months, 74% of all study participants (n = 1493) had discontinued antipsychotic treatment. Despite the variability reported in the literature, the rates of non-adherence in patients with schizophrenia are at least similar to those of patients with other chronic illnesses.²⁶

Impact of non-adherence

The impact of non-adherence to antipsychotic treatment for individuals with schizophrenia is likely the intensification of the severity of positive symptoms that, many times, will lead to a corresponding hospitalization. Multiple studies have shown that non- adherence is associated with higher rates of readmission, longer lengths of stay, and higher costs.^28-30 Weiden et al³⁰ used medication possession ratios (i.e., the percentage of time a patient has access to medication) to study the relationship between antipsychotic treatment adherence and risk of rehospitalization for patients (n = 4325) with schizophrenia who were participants in the California Medicaid program. Patients who were adherent at least 70% of the time were found to have lower hospitalization rates during the 1-year study period than patients who had lower adherence rates (13.8% vs. 22.3%, p < 0.001). Similarly, a recent study by Hardy et al³¹ reported that individuals who had a medication possession ratio below 0.8 had a 1.61-times higher risk for emergency department use than patients with higher medication possession ratios.

In addition to the risk for rehospitalization, there are also psychosocial and biological issues related to relapse.³² Psychosocially, there is a risk of patients jeopardizing personal relationships, education, employment status, and social supports. Biologically, acute psychosis may be a neurotoxic event that is damaging to the brain. It may also represent disease progression and/or may pose a risk of patients not regaining their previous levels of functioning and developing treatment refractoriness. Therefore, the values of minimizing acute illness relapses in schizophrenia are the optimization of a patient's long-term functioning and the prevention of his or her illness from worsening. Unfortunately, the majority of individuals living with schizophrenia experience multiple relapses over the course of their illness.³²

BARRIERS TO TREATMENT ADHERENCE IN SCHIZOPHRENIA

Achieving treatment adherence for individuals with schizophrenia is challenging. While there are likely many reasons why treatment non-adherence exists, the risk may begin when providers do not spend an adequate amount of time assessing adherence and when patients are not transparent about their medication-taking intentions.²⁶ Risk factors identified for treatment non-adherence to antipsychotics include adverse medication effects, comorbid substance use disorder, severe symptoms of schizophrenia, poor level of functioning, and financial difficulties.³³ Other factors may include younger age, poor insight, cognitive impairments, low level of education, minority ethnicity, poor therapeutic alliances, experiencing barriers to care, high intensity of delusional symptoms and suspiciousness, and low socioeconomic status.³⁴

Adverse medication effects

All antipsychotics are associated with risks of routine adverse effects, as well as serious, but rare, adverse effects. Table 1 summarizes the relative frequencies of routinely anticipated adverse effects to selected antipsychotic treatment.³ Sedation, orthostasis, and anticholinergic effects are important routine monitoring parameters, and tardive dyskinesia and weight gain are high-priority monitoring parameters.³ Tardive dyskinesia, while relatively more likely to occur with first-generation antipsychotics than with second-generation antipsychotics, is an infrequent condition, but it is potentially irreversible. Consequently, the emergence of any abnormal involuntary movements in a patient receiving antipsychotic therapy is cause for concern and, likely, a re-evaluation of the acceptability of the patient's current antipsychotic therapy. The concern about weight gain in schizophrenia is directly related to the development of metabolic syndrome, diabetes, and cardiovascular disease. It has been well described that individuals living with schizophrenia live much shorter lives than people without schizophrenia, largely due to the impact of cardiovascular illnesses.³

Other important adverse effects of antipsychotics include QT prolongation; neuroleptic malignant syndrome; hematological manifestations such as leukopenia, neutropenia, and agranulocytosis; and seizures. Since these are not experienced by most patients with schizophrenia who are treated with antipsychotics, it is important to evaluate each patient's risk factors for these effects on a case-by-case basis.³

Barriers to treatment adherence in community pharmacy

The community pharmacist can be a key component of a patient's support system by identifying barriers to and assisting with treatment adherence. High prescription volumes that require pharmacist time and attention, lack of privacy for counseling patients about sensitive illness-related issues, and a pharmacist's lack of training about how best to support patients with mental illness may be barriers to pharmacist engagement with individuals living with schizophrenia.^36,37 In addition, patients may encounter the barrier of mental illness stigma in the healthcare system, including within community pharmacy settings.³⁶ Stigma is a negative attitude that one individual has towards another, and, in the healthcare system, it can be triggered by an illness marker (e.g., a dispensed psychotropic medication). Stigma is an important source of discrimination that patients with mental health conditions experience.³⁸ Ultimately, patients who are stigmatized experience barriers to care that increase their risks for treatment non-adherence, poor treatment outcomes, and shorter lifespans.^39,40 These individuals also report that stigma is a barrier to recovery because of the negative effects it has on social status, self-esteem, and social networking.^38-44

TREATMENT APPROACHES TO SCHIZOPHRENIA

The availability of oral antipsychotics dates back to the discovery of chlorpromazine in the 1950s. Unfortunately, patients treated with any oral antipsychotic experience substantial rates of treatment non-adherence. Consequently, efforts have been made to identify alternative treatment strategies to improve outcomes through treatment adherence in patients with schizophrenia. Long-acting injectable antipsychotics (LAIAs) have been available for decades, and, although their rate of use has been low, the growing number of available treatments permits greater opportunities for improved outcomes related to non-adherence with oral antipsychotics.

Injectable antipsychotics

Injectable antipsychotics exist in 2 distinct categories: immediate (or short) acting and long acting. Immediate-acting antipsychotics are administered intramuscularly to treat symptoms of acute psychosis related to schizophrenia and other psychiatric illnesses (e.g., bipolar I mania). Examples of immediate-acting agents include haloperidol lactate (5 mg/mL), olanzapine (5 mg/mL), and ziprasidone mesylate (20 mg/mL).^45-47 These injectable antipsychotics require the use of doses similar to their oral counterparts and the durations of effect are similar, as well.

Case, continued AB has participated in the IOP for 3 weeks, and, now, his psychiatrist proposes to consider long-acting paliperidone injections once every 4 weeks (in place of oral paliperidone) given his history of episodic treatment non-adherence, the effectiveness of his current oral paliperidone regimen, and his goal of becoming re-employed. AB agrees to this treatment approach because he was working while being treated with olanzapine in the past and he does not wish to jeopardize any future employment opportunities.

LAIAs can have significant roles in the maintenance treatment of schizophrenia and, ideally, in the prevention of symptomatic relapse and re-hospitalization. These dose forms (Table 2) incorporate high-potency antipsychotics into either an oil-based or aqueous-based vehicle, which allows for slow absorption from the injection site. Doses for LAIAs are typically much higher than for their oral counterparts, and the injections are given once every 2 to 12 weeks, depending on which antipsychotic formulation is being administered. Prior to commencing LAIA treatment, it is best for patients to establish safety and efficacy with the oral formulation of the antipsychotic.³

Pharmacokinetic considerations are paramount for LAIAs: absorption time for an LAIA dose is much longer than the time needed for its metabolism, which is opposite from the pharmacokinetics of oral medications. Consequently, the "half-life" used to estimate time to steady state and time to complete elimination from the body is the LAIA's dosing interval. For example, an LAIA dosed once every 4 weeks will be at steady state after the fifth injection, or at 20 weeks. Therefore, a substantial amount of time is required to judge the clinical impact of any dose changes (increases or decreases) made during treatment. Patients, pharmacists, and providers must be aware of this characteristic, since an immediate impact cannot be expected from an increased dose of a very slowly absorbed dose form.

Haloperidol decanoate and fluphenazine decanoate

The United States Food and Drug Administration (FDA) has approved 2 long-acting forms of first-generation antipsychotics, each is a decanoate in a sesame oil vehicle. Because of the oil vehicle, a Z-track method is recommended for administration of the injection in order to minimize leakage of medication back through the injection site. A 0.1-mL test dose is advised 24 to 48 hours before treatment initiation with either of these agents because patients may have an unknown allergy to sesame.

Haloperidol decanoate⁴⁸ is a butyrophenone-type antipsychotic with potent D2 receptor antagonism and minimal additional pharmacological characteristics. It has a dosing interval of 4 weeks, and it is metabolized by cytochrome P450 (CYP) isoenzymes 1A2, 2D6, and 3A4.³ Dosing of haloperidol decanoate is best determined using the total daily dose of oral haloperidol effective for the individual patient multiplied by a factor of 10 to 20. When a loading-dose strategy is desired, the oral dose is multiplied by 20 for the first dose, by 15 for the second dose, and by 10 for the third and subsequent doses. Alternatively, the oral haloperidol dose may be multiplied by 10 to 15 to determine the patient's maintenance dose of the decanoate. Daily oral haloperidol is not required at the beginning of haloperidol decanoate treatment.

Fluphenazine is a phenothiazine-type antipsychotic that is also a potent D2 receptor antagonist; it has some affinity for histamine-1, alpha-1, and muscarinic-1 receptors, which may cause sedation, orthostasis, and anticholinergic effects (e.g., dry mouth, constipation) for patients.³ Fluphenazine decanoate is usually dosed once every 2 to 3 weeks and it is metabolized by CYP2D6.⁴⁹ Dosing fluphenazine decanoate requires multiplying the total daily oral dose by 1.2. There is no loading dose option and daily oral fluphenazine overlap is not required when initiating injectable treatment.

Both haloperidol and fluphenazine place patients at risk for experiencing extrapyramidal symptoms (EPS; e.g., akathisia, parkinsonism), and patients receiving either of these treatments should be routinely monitored for EPS. The emergence of any movement- related side effect should prompt the pharmacist to communicate with the patient's provider and discuss the need for EPS management.

Risperidone microspheres and risperidone suspension

Risperidone microspheres (Risperdal Consta)⁵⁰ was the first second-generation antipsychotic to be marketed in a long-acting injectable form. Risperidone microspheres are incorporated into a matrix and then suspended in an aqueous vehicle. This product must be stored under refrigeration. The pharmacology of risperidone includes D2, 5- HT2A, alpha-1, alpha-2, and histamine-1 receptor antagonism.⁵⁰ Risperidone is metabolized by CYP2D6 and it has an active metabolite (9-hydroxy-risperidone, also known as paliperidone) that has a similar pharmacology to risperidone.

The absorption of risperidone microspheres is unique. Following each injection, it takes approximately 3 weeks for risperidone to begin appearing in circulation.⁵⁰ Accordingly, daily oral risperidone treatment is required for 3 weeks following the first injection. Injections are administered every 2 weeks. Risperidone microsphere dosing is based on the effective oral risperidone dose. When a patient is receiving less than 3 mg daily of oral risperidone, the first intramuscular dose of microspheres is 25 mg; a daily dose of 3 to 5 mg of oral risperidone converts to 37.5 mg; and a daily dose greater than 5 mg converts to 50 mg.⁵¹ Adverse effects of risperidone include a risk of EPS, hyperprolactinemia, orthostasis, and a risk for developing signs of metabolic syndrome.

Perseris is a recently approved long-acting risperidone suspension dose form that is administered subcutaneously in a patient's abdomen. No other LAIA product is administered by this route. Patients receive either 90 mg (corresponding to 3 mg/day orally) or 120 mg (corresponding to 4 mg/day orally) once every 4 weeks. Oral risperidone treatment overlap is not advised. For this dose form, risperidone is present in a lactide-glycolide polymer that, once injected, delivers 2 peak serum concentrations: the first peak occurs within 4 to 6 hours of the injection, and the second peak occurs 10 to 14 days after injection.⁵²

Case, continued Due to limited outpatient medication administration services through the IOP, the psychiatrist proposes to AB that they work with a local community pharmacist who offers LAIA injection services. After AB discusses and agrees to the plan, the psychiatrist contacts the local community pharmacist and sets up an appointment for AB to receive his first paliperidone palmitate injection.

Paliperidone palmitate

Paliperidone is also known as 9-hydroxy-risperidone and it is the active metabolite of risperidone. Paliperidone palmitate is available in 2 forms: Invega Sustenna⁵³ and Invega Trinza.⁵⁴ The pharmacokinetics of paliperidone palmitate (Invega Sustenna) allow it to be dosed once every 4 weeks; a peak plasma concentration occurs 13 days after the injection. Metabolism by CYP3A4 and unchanged renal elimination are primarily responsible for its clearance. Patients treated with paliperidone palmitate receive a first injection of 234 mg and then, 7 days later, receive a second injection of 156 mg. (This is referred to as initiation dosing) Four weeks after the second injection, a third injection is administered at a dose determined by the effective oral paliperidone dose: 3 mg oral paliperidone corresponds to 39 mg or 78 mg intramuscular paliperidone palmitate; 6 mg oral corresponds to 117 mg intramuscular; 9 mg oral corresponds to 156 mg intramuscular; and 12 mg oral corresponds to 234 mg intramuscular. No oral paliperidone overlap dosing is required.⁵³

Paliperidone palmitate (Invega Trinza)⁵⁴ is designed to be administered once every 12 weeks; the peak plasma concentration of this form occurs between 30 and 33 days after injection. In order for this form of paliperidone palmitate to be used, patients are required to have received at least 4 consecutive monthly injections of Invega Sustenna. Invega Trinza doses are then determined by the Invega Sustenna doses that were administered: 78 mg Sustenna corresponds to 273 mg Trinza; 117 mg Sustenna corresponds to 410 mg Trinza; 156 mg Sustenna corresponds to 546 mg Trinza; and 234 mg Sustenna corresponds to 819 mg Trinza. Adverse effects of paliperidone are similar to risperidone and include a risk for EPS, hyperprolactinemia, orthostasis, and metabolic syndrome.⁵⁴

Aripiprazole lauroxil and aripiprazole monohydrate

Aripiprazole, which has a broad pharmacology, is primarily considered a partial D2 receptor agonist-type atypical antipsychotic. This means it achieves its reduction in dopamine activity by stimulating D2 receptors at a signal strength that is only a fraction of what dopamine generates. Additionally, aripiprazole is a 5-HT2A receptor antagonist and a partial 5-HT1A receptor agonist. It is metabolized by both CYP2D6 and CYP3A4.

Aripiprazole is available in 2 long-acting injectable products. Aripiprazole lauroxil (Aristada,⁵⁵ Aristada Initio⁵⁶) is a prodrug for aripiprazole and, after administration, is converted to N-hydroxymethyl aripiprazole, which is then converted to aripiprazole. Aristada Initio (aripiprazole lauroxil 675 mg) was approved in July 2018⁵⁷ as an injectable "initiation" dose form for the "maintenance" Aristada dose form. Prior to the approval of Aristada Initio, patients treated with Aristada were required to also be treated with 3 weeks of daily oral aripiprazole after receiving the first injection. With the Initio dose form, patients who are administered the first Aristada injection (at a dose corresponding to their oral aripiprazole dose) may then have an Initio dose administered and then also ingest a single oral 30-mg aripiprazole dose. This treatment initiation is an alternative to the 3-week oral aripiprazole overlap requirement.⁵⁷

Maintenance Aristada is recommended to be dosed using the effective oral aripiprazole dose as a guide and injections are administered once every 4 to 8 weeks: 10 mg oral aripiprazole corresponds to 441 mg aripiprazole lauroxil every 4 weeks; 15 mg oral aripiprazole corresponds to 662 mg aripiprazole lauroxil every 4 weeks, 882 mg every 6 weeks, or 1064 mg every 8 weeks; and 20 mg oral aripiprazole corresponds to 882 mg aripiprazole lauroxil every 4 weeks. Adverse effects of aripiprazole include risks for developing compulsive behaviors, EPS (especially akathisia/restlessness), and metabolic syndrome.

Aripiprazole monohydrate (Abilify Maintena) was the first long-acting aripiprazole product approved by the FDA. It is also administered once every 4 weeks.⁵⁸ Dosing of aripiprazole monohydrate is less dependent on the effective oral aripiprazole dose and, for most patients, the starting and maintenance doses of aripiprazole monohydrate should be 400 mg. Fourteen days of oral aripiprazole overlap is required for aripiprazole monohydrate, and there is no injectable initiation dose alternative as there is with aripiprazole lauroxil.

Olanzapine pamoate

Olanzapine is a potent 5-HT2A antagonist and a D2 receptor antagonist, as well as a clinically important histamine-1 antagonist and muscarinic-1 antagonist. Olanzapine pamoate (Zyprexa Relprevv)⁵⁹ has a pharmacokinetic profile that permits it to be administered once every 2 or 4 weeks, and peak plasma concentrations occur within the first week following an injection. The dose range is 150 to 300 mg every 2 weeks to 300 to 405 mg every 4 weeks. Two key determinants of olanzapine pamoate dosing are 1) the effective oral olanzapine dose and 2) whether the patient is within, or beyond, the first 8 weeks of olanzapine pamoate treatment. In addition to the common adverse effects associated with olanzapine pamoate treatment (i.e., sedation, headache, increased appetite, weight gain, metabolic syndrome), patients are also at risk for post- injection delirium/sedation syndrome.⁵⁹ Patients who experience this toxicity develop signs and symptoms consistent with an olanzapine overdose (sedation, coma, and/or delirium). These events were reported in 2% of patients who received injections over a 46-month period during clinical trials.⁵⁹ Despite the low frequency of this event, use of olanzapine pamoate requires that all patients be monitored for this syndrome at a healthcare facility by a healthcare professional for a minimum of 3 hours after each injection.

KEY CONSIDERATIONS FOR THE ADMINISTRATION OF LONG-ACTING ANTIPSYCHOTICS

Pharmacists who decide to provide LAIA administration to patients with schizophrenia must be prepared to offer an effective service. The first steps in developing this service are to ensure that all required LAIA training (as determined by state regulations) is acquired and to guarantee that a stigma-free environment with available private space is provided. Pharmacists also need to choose which LAIAs will be administered as part of the service. For example, it is unlikely that community pharmacies will offer olanzapine pamoate injections given the requirements of being an approved healthcare facility and the need for at least 3 hours of monitoring after each administered injection. Additionally, pharmacists must complete training specific to the antipsychotics they wish to administer. For example, the long-acting first-generation antipsychotics, such as haloperidol decanoate, require a different administration method than the one used for second-generation injectable antipsychotics. Other issues that pharmacists must consider include LAIA storage requirements, proper needle selection, the need to rotate injection sites, the administration of gluteal injections, the availability of a chaperone for injections (chaperones may not be required but may be desired by the patient or the pharmacist), the need to review patient's concurrent pharmacotherapy for pharmacokinetic and/or pharmacodynamic interactions, the need for documentation of services, and the need for communication of service delivery back to the patient's mental healthcare provider. Pharmacy staff will also need to understand the procedures for provision of administration services, ranging from routine scheduling of patients to what happens when a patient presents for an injection without an appointment.

Once training and preparation have been completed, the pharmacist may advertise to local mental healthcare providers that an LAIA service is offered. Pharmacists interested in learning more about mental illness and psychotropic medications can consider becoming certified in Mental Health First Aid⁶⁰ and can access the medication information documents authored by psychiatric pharmacists on the website of the National Alliance on Mental Illness.⁶¹

PHARMACISTS' ROLES IN MANAGING SCHIZOPHRENIA

Pharmacy's pursuit of an increased role in patient care began with the clinical pharmacy movement in the 1960s. In the 1990s, community pharmacists expanded their patient care efforts by becoming involved in vaccine administration. Since that time, the extent to which community pharmacists have become involved in patient care has grown to a point where nearly all are trained to administer vaccinations and offer this service as part of their routine pharmacy practice.⁶²

This same time period has seen substantial rates of treatment non-adherence for patients with schizophrenia, as well as the expansion of the number of LAIAs that are available. Additionally, outpatient medication administration services within the mental healthcare system have been reported to be inconsistently available,⁶² which has created a need for additional medication administration services. Community pharmacists, who are more accessible than other healthcare providers,⁶² have opportunities to meet the needs of patients in the mental healthcare system by offering medication administration services.

An important consideration for community pharmacists who are interested in delivering LAIA administration services is what each state pharmacy practice act permits with respect to medication administration services. While all states permit pharmacists to administer vaccines, not all states permit pharmacists to administer other medications. According to a January 2018 report by the National Community Pharmacists Association, 28 states permit pharmacists to administer LAIAs in an unrestricted manner, 7 states require pharmacists to have a collaborative practice agreement with a psychiatrist in order to administer LAIAs, and 15 states plus the District of Columbia do not permit pharmacists to administer LAIAs (Table 3).⁶³ Pharmacists practicing in states that permit them to administer LAIAs should not only completely understand the laws governing this service but should also be aware of the eligibility and competency requirements related to the service.

Regardless of the need for a collaborative practice agreement, pharmacists who administer LAIA injections should understand that they are participating in chronic care, since they will be administering injections to patients on a routine basis. As such, pharmacists are responsible for documenting and communicating with a patient's provider each time a service is delivered. A pharmacist must also communicate if a patient does not appear for a scheduled appointment or is early or late for an injection. Additionally, pharmacists need to establish and maintain therapeutic relationships with patients so that they may accurately assess efficacy and tolerability of the treatments.

Case, continued: On the day before AB is to receive his first paliperidone palmitate injection, he receives a phone call from the community pharmacy reminding him of his appointment. The next day, AB arrives on time for his first injection. He is greeted in a professional manner by the pharmacy technician who was already aware of the appointment. The technician confirms the patient's identity and provides him with educational information about his paliperidone injection. AB is brought to the pharmacy's private room by the technician and is asked to review the information and sign a consent document that confirms his willingness to receive a paliperidone palmitate injection from the community pharmacist. The pharmacist and technician return to the room with supplies to prepare the injection. Prior to preparing the injection, the pharmacist sits down with the patient and introduces himself and asks AB if he has any questions. The pharmacist asks about AB's symptoms and whether or not he has been experiencing any adverse medication effects; he also confirms the patient's current medications. Once their discussion is complete, the pharmacist asks the technician to remain with him during the injection as a "chaperone" and confirms with AB that he will be receiving his injection in the right deltoid. The pharmacist then prepares the paliperidone palmitate 234 mg injection. Using proper technique, the pharmacist administers the injection and then asks AB to remain for a few moments to make sure that there are no problems related to the injection. After 10 minutes, AB reports that he is feeling fine. The pharmacist then informs the patient that he does not need to continue his oral paliperidone treatment and that he needs to return to the pharmacy in 7 days for his next injection of paliperidone palmitate 156 mg. AB receives an appointment reminder card to take with him. After AB has left the pharmacy, the pharmacist completes his documentation of the service provided and faxes the documentation directly to the psychiatrist at the IOP with an offer to answer any questions that the psychiatrist might have.

REFERENCES

1. Krystal JH, Anticevic A. Toward illness phase-specific pharmacotherapy for schizophrenia. Biol Psychiatry. 2015;78(11):738-40.
2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Publishing; 2013.
3. Crismon ML, Kattura RS, Buckley PF. Schizophrenia. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill Education; 2016.
4. Javed A, Charles A. The importance of social cognition in improving functional outcomes in schizophrenia. Front Psychiatry. 2018;9:157.
5. Macek TA, McCue M, Dong X, et al. A phase-2, randomized, placebo-controlled study of the efficacy and safety of TAK-063 in subjects with an acute exacerbation of schizophrenia. Schiz Res. 2018. pii: S0920-9964(18)30540-1.
6. Trivedi MH, Rush AJ, Wisniewski SR, et al; STAR*D Study Team. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006;163(1):28-40.
7. Kurachi M, Takahashi T, Sumiyoshi T, et al. Early intervention and direction of novel therapeutics for the improvement of functional outcomes in schizophrenia: a selective review. Front Psychiatry. 2018;9:39.
8. Csernansky JG, Mahmoud R, Brenner R; Risperidone-USA-79 Study Group. A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia. N Engl J Med. 2002;346(1):16-22.
9. Lacro JP, Dunn LB, Dolder CR, et al. Prevalence of and risk factors for medication nonadherence in patients with schizophrenia: a comprehensive review of recent literature. J Clin Psychiatry. 2002;63(1):892-909.
10. Kasper S, Lerman MN, McQuade RD, et al. Efficacy and safety of aripiprazole vs. haloperidol for long-term maintenance treatment following acute relapse of schizophrenia. Int J Neuropsychopharmacol. 2003;6(4):325-37.
11. Nosé M, Barbui C, Tansella M. How often do patients with psychosis fail to adhere to treatment programmes? A systematic review. Psychol Med. 2003;33(7):1149-60.
12. Gilmer TP, Dolder CR, Lacro JP, et al. Adherence to treatment with antipsychotic medication and health care costs among Medicaid beneficiaries with schizophrenia. Am J Psychiatry. 2004;161(4):692-9.
13. Valenstein M, Blow FC, Copeland LA, et al. Poor antipsychotic adherence among patients with schizophrenia: medication and patient factors. Schizophr Bull. 2004; 30(2):255-64.
14. Schooler N, Rabinowitz J, Davidson M, et al; Early Psychosis Global Working Group. Risperidone and haloperidol in first-episode psychosis: a long-term randomized trial. Am J Psychiatry. 2005;162(5):947-53.
15. Valenstein M, Ganoczy D, McCarthy JF, et al. Antipsychotic adherence over time among patients receiving treatment for schizophrenia: a retrospective review. J Clin Psychiatry. 2006;67(10):1542-50.
16. Gaebel W, Riesbeck M, Wölwer W, et al; German Study Group on First-Episode Schizophrenia. Maintenance treatment with risperidone or low-dose haloperidol in first-episode schizophrenia: 1-year results of a randomized controlled trial within the German Research Network on Schizophrenia. J Clin Psychiatry. 2007;68(11):1763-74.
17. Keks NA, Ingham M, Khan A, Karcher K. Long-acting injectable risperidone v. olanzapine tablets for schizophrenia or schizoaffective disorder. Randomised, controlled, open-label study. Br J Psychiatry. 2007;191:131-9.
18. Kahn RS, Fleischhacker WW, Boter H, et al; EUFEST study group. Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet. 2008;371(9618):1085-97.
19. Perkins DO, Gu H, Weiden PJ, et al; Comparison of Atypicals in First Episode study group. Predictors of treatment discontinuation and medication nonadherence in patients recovering from a first episode of schizophrenia, schizophreniform disorder, or schizoaffective disorder: a randomized, double-blind, flexible-dose, multicenter study. J Clin Psychiatry. 2008;69(1):106-13.
20. Dassa D, Boyer L, Benoit M, et al. Factors associated with medication non-adherence in patients suffering from schizophrenia: a cross-sectional study in a universal coverage health-care system. Aust N Z J Psychiatry. 2010;44(1):921-8.
21. Gaebel W, Schreiner A, Bergmans P, et al. Relapse prevention in schizophrenia and schizoaffective disorder with risperidone long-acting injectable vs quetiapine: results of a long-term, open-label, randomized clinical trial. Neuropsychopharmacology. 2010;35(12):2367-77.
22. Jónsdóttir H, Opjordsmoen S, Birkenaes AB, et al. Medication adherence in outpatients with severe mental disorders: relation between self-reports and serum level. J Clin Psychopharmacol. 2010;30(2):169-75.
23. Dibonaventura M, Gabriel S, Dupclay L, et al. A patient perspective of the impact of medication side effects on adherence: results of a cross-sectional nationwide survey of patients with schizophrenia. BMC Psychiatry. 2012;12:20.
24. Adelufosi AO, Adebowale TO, Abayomi O, Mosanya JT. Medication adherence and quality of life among Nigerian outpatients with schizophrenia. Gen Hosp Psychiatry. 2012;34(1):72-9.
25. Waterreus A, Morgan VA, Castle D, et al. Medication for psychosis – consumption and consequences: the second Australian national survey of psychosis. Aust N Z J Psychiatry. 2012;46(8):762-73.
26. Kane JM, Kishimoto T, Correll CU. Non-adherence to medication in patients with psychotic disorders: epidemiology, contributing factors and management strategies. World Psychiatry. 2013;12(3):216-26.
27. Lieberman JA, Stroup TS, McEvoy JP, et al; Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. New Engl J Med. 2005;353(12):1209-23.
28. Jiang Y, Ni W. Estimating the impact of adherence to and persistence with atypical antipsychotic therapy on health care costs and risk of hospitalization. Pharmacotherapy. 2015;35(9):813-22.
29. Offord S, Lin J, Wong B, et al. Impact of oral antipsychotic medication adherence on healthcare resource utilization among schizophrenia patients with Medicare coverage. Community Ment Health J. 2013;49(6):625-29.
30. Weiden PJ, Kozma C, Grogg A, Locklear J. Partial compliance and risk of rehospitalization among California Medicaid patients with schizophrenia. Psychiatr Serv. 2004;55(8):886-91.
31. Hardy M, Jackson C, Byrne J. Antipsychotic adherence and emergency department utilization among patients with schizophrenia. Schizophr Res. 2018. pii: S0920-9964(18)30339-6.
32. Emsley R, Chiliza B, Asmal L, Harvey BH. The nature of relapse in schizophrenia. BMC Psychiatry. 2013;13:50.
33. Compton MT, Rudisch BE, Weiss PS, et al. Predictors of psychiatrist-reported treatment compliance problems among patients in routine U.S. psychiatric care. Psych Res. 2005;137(1-2):29-36.
34. Garcia A, Martinez-Cengotitabengoa M, López-Zurbano S, et al. Adherence to antipsychotic medication in bipolar disorder and schizophrenic patients: a systematic review. J Clin Psychopharmacol. 2016;36(4):355-71.
35. Calogero S, Caley CF. Supporting patients with mental illness: deconstructing barriers to community pharmacist access. J Am Pharm Assoc (2003). 2017;57(2):248-55.
36. Giannetti V, Caley CF, Kamal KM, et al. Community pharmacists and mental illness: a survey of service provision, stigma, attitudes and beliefs. Int J Clin Pharm. 2018.
37. Sartorius N. Stigma and mental health. Lancet. 2007;370(9590):810-1.
38. Thornicroft G. Most people with MI are not treated. Lancet. 2007;370(9590):807-8.
39. Barney LJ, Griffiths KM, Jorm AF, Christensen H. Stigma about depression and its impact on help-seeking intentions. Aust N Z J Psychiatry. 2006;40(1):51-4.
40. Gardner DM, Murphy AL, Woodman AK, Connelly S. Community pharmacy services for antidepressant users. Int J Pharm Pract. 2001;9(4):217-24.
41. Hoch MA, Ott CA, Hudmon KS, Plake KS. Attitudes of individuals with schizophrenia towards pharmacists. J Am Pharm Assoc (2003). 2012;52(6):783-6.
42. Knox K, Fezjic J, Mey A, et al. Mental health consumer and caregiver perceptions of stigma in Australian community pharmacies. Int J Soc Psychiatry. 2014;60(6):533-43.
43. Consumer and carer experiences of stigma from mental health and other health professionals. Mental Health Council of Australia. https://mhaustralia.org/sites/default/files/imported/component/rsfiles/ stigma/Consumer_and_Carer_Experiences_of_Stigma_from_Mental_Health_and_Other_Health_Professionals.pdf. Published 2011. Accessed September 26, 2018.
44. Haldol (haloperidol lactate) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2017.
45. Zyprexa [prescribing information]. Indianapolis, IN: Lilly USA, LLC; 2018.
46. Geodon [prescribing information]. New York, NY: Pfizer, Inc.; 2015.
47. Haldol (haloperidol decanoate) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2017.
48. Fluphenazine decanoate [prescribing information]. Eatontown, NJ: West-Ward Pharmaceuticals; 2016.
49. Risperdal Consta [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2018.
50. Bai YM, Ting Chen T, Chen JY, et al. Equivalent switching dose from oral risperidone to risperidone long-acting injection: a 48-week randomized, prospective, single-blind pharmacokinetic study. J Clin Psychiatry. 2007;68(8):1218-25.
51. Perseris [prescribing information]. North Chesterfield, VA: Indivior, Inc.; 2018.
52. Invega Sustenna [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2018.
53. Invega Trinza [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2018.
54. Aristada [prescribing information]. Waltham, MA: Alkermes, Inc.; 2018.
55. Aristada Initio [prescribing information]. Waltham, MA: Alkermes, Inc.; 2018.
56. FDA approves ARISTADA INITIO for the initiation of ARISTADA for schizophrenia. https://www.prnewswire.com/news-releases/fda-approves-aristada-initio-for-the-initiation-of-aristada-for-schizophrenia-300675138.html. Published July 2, 2018. Accessed September 27, 2018.
57. Abilify Maintena [prescribing information]. Rockville, MD: Otsuka America Pharmaceutical, Inc.; 2018.
58. Zyprexa Relprevv [prescribing information]. Indianapolis, IN: Lilly USA, LLC.; 2018.
59. Mental Health First Aid USA. https://www.mentalhealthfirstaid.org. Accessed October 2, 2018.
60. Types of medication. National Alliance on Mental Illness. https://www.nami.org/Learn-More/Treatment/Mental-Health-Medications/Types-of-Medication. Reviewed August 2017. Accessed October 2, 2018.
61. State policy recommendations for pharmacist administration of medications: A report from the stakeholder group convened by the National Alliance of State Pharmacy Associations and the College of Psychiatric and Neurologic Pharmacists. https://naspa.us/wp-content/uploads/2017/04/Medication-Administration-Meeting-Report-FINAL.pdf. Published March 2017. Accessed October 19, 2018.
62. Administration of long-acting injectable antipsychotic medications. National Community Pharmacists Association. https://www.ncpanet.org/innovation-center/diversified-revenue-opportunities/administration-of-long-acting-injectable. Updated January 2018. Accessed October 3, 2018.

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