by Alvaro Camacho, MD; Bernardo Ng, MD; Barbara Galangue, MA; David Feifel, MD, PhD

Drs. Camacho and Ng are with the Imperial County Behavioral Health, El Centro, California, the Sun Valley Research Center, Imperial, California, and the Department of Psychiatry. University of California, San Diego; Ms. Galangue and Dr. Feifel are with the Department of Psychiatry. University of California, San Diego.


Background: The rate of medication nonadherence among patients with chronic psychiatric conditions, such as schizophrenia and bipolar disorder, has been estimated to be between 40 and 60 percent. Poor adherence leads to clinical deterioration and increased disability in this population. Additionally, it adds to the burden cost of providing mental health services in underserved rural areas. Long-term injectable antipsychotics are considered a valuable tool to counteract medication nonadherence.

Objective: To describe the level of adherence and functioning among a group of patients, the majority of which were Hispanic, receiving risperidone long acting injectable (RLAI) in a community clinic in a border area of rural southern California.

Methodology: A retrospective chart review was conducted from January, 2005, though December, 2006, of patients receiving RLAI, looking at adherence to their scheduled appointments and improvement in their global assessment of functioning (GAF).

Results: Fifty patients with schizophrenia and bipolar disorder were reviewed. Thirty-four received RLAI for at least one year, seven for at least six months, and seven for at least three months. For patients receiving RLAI, there was a significant improvement in patient adherence with appointments. Their no-show rate improved from 27 to 15 percent. Similar improvement was found for those patients receiving RLAI for six and three months. For those patients receiving RLAI for one year, their GAF improved from a mean of 40.8 to 57.2 (standard deviation [SD]=12.39, df=33, p<0.01). Similar improvement was found in those receiving RLAI for six months (mean GAF improvement from 36.4 to 51.8 [SD=9.7, df=6, p<0.01]) and three months (mean GAF improvement from 40.7–60.4 [SD=13.8, df=6, p<0.01]).

Conclusion: Adherence among our group of majority Hispanics with disabling psychiatric conditions (schizophrenia and severe bipolar disorder) improved when they participate in a RLAI clinic with active case management. A longitudinal follow-up study is needed to determine improvement of their quality of life, comorbid substance use, and metabolic outcomes, and to evaluate long-term remission of symptoms among this specific population.

Key Words

Hispanics, risperidone long-acting injectable, border rural area

Schizophrenia and bipolar disorders are chronic, disabling, and costly neuropsychiatric conditions that currently affect approximately one percent and five percent of the US population, respectively.[1–4] Recent reports have described rates as high as 18 percent of presumed psychotic symptoms among Mexican-Americans.[5] The expenses associated with the treatment of patients with schizophrenia were calculated close to $34 billion in 1990, which included repetitive hospitalizations and decreased productivity.[6] Similarly, conditions within the bipolar spectrum are considered to be one of the most expensive medical entities to treat.[7,8] Peele, et al., found that patients with bipolar disorder spend more than double in out-of-pocket expenses for their care. Moreover, the authors found that patients with bipolar disorder have higher hospitalization rates (40% more) compared to any other insurance claim for behavioral healthcare.[8]

The course of the illness varies, but there are frequent relapses that might be a predictor of future refractoriness to treatment and increased disability.[9] Studies have shown that the main factor for relapse is the partial or nonadherence with antipsychotic treatment.[10,11] Based on published data, close to 60 percent of individuals with schizophrenia are nonadherent with treatment.[12,13] Among patients with bipolar disorder, rate of nonadherence has been reported to be close to 50 percent.[14] Studies have also reported that the risk of relapse in patients with schizophrenia is approximately 3.5 percent per month.[15] Common factors that account for the rate of relapse are poor insight into their illness, poor relationship between patients and health providers, and comorbid substance abuse.

Kavanagh and coworkers studied a sample of 852 patients with psychosis. They found that 40 percent of patients with a first-time diagnosis of psychosis had an ongoing substance abuse problem. The most commonly misused substance was alcohol (27%), followed by cannabis (26%) and amphetamines (17%).[16] Green and his group reported that patients with substance use disorders have greater periods of untreated psychosis before they receive their first diagnosis of schizophrenia or similar psychotic disorders. The authors emphasized the importance of recognizing that these patients could have worse outcomes of their psychosis and more refractoriness to treatment if they are not treated promptly.[17]

The use of long-acting injectable antipsychotics (LAIA) was introduced in 1960s in an attempt to reduce problems with adherence, deterioration of quality of life, and repetitive hospitalizations. Long-acting injectable formulations of first generation antipsychotics enjoyed significant success and were considered useful tools to address nonadherence in schizophrenia patients. Moreover, they were shown to be a cost-effective approach in the treatment of schizophrenia and related psychotic disorders.[18–20]

Second-generation antipsychotic drugs, also known as atypical antipsychotics, emerged in the early 1990s and were demonstrated to be effective in preventing relapse and improving quality of life in patients suffering from schizophrenia and other related thought disorders.1 Additionally, these medications tend to have fewer adverse effects than first-generation antipsychotics, especially pseudoparkinsonism and akathisia.[21,22] However, until recently, second generation antipsychotics were not available in a long-acting injectable formulation.

Risperidone long-acting injectable (RLAI) was introduced first in England in 2002 and entered the US marketplace in 2003.[23] It represents the first long-acting injectable formulation of a second generation antipsychotic. Data suggest it has a well-demonstrated record of safety and effectiveness.[20,24] Edwards and colleagues reviewed the literature on existing consumer health databases and found that the rate of re-hospitalizations in patients taking LAIA antipsychotics was 26 percent with long-acting risperidone compared to 60 percent in those patients taking LAIA haloperidol and 41 percent in those patients taking oral new generation antipsychotics after a year of treatment.[25] Additionally, they found that the mean days of hospitalization per patient per year were 28 with LAIA haloperidol, 18 for oral new generation antipsychotic, and 11 for patients taking long-acting risperidone. Furthermore, the direct medical costs in dollars were 161 for long-acting risperidone, 1,425 for oral risperidone, 508 for olanzapine, and 2,334 for LAIA haloperidol.[26]

In order to further assess the potential impact of RLAI on chronically ill patients with poor adherence, we decided to conduct a retrospective chart review to assess the level of adherence and changes in their Global Assessment of Functioning (GAF) in a group of patients receiving RLAI who were attending a rural community clinic. This facility is located in Imperial County, California, which is the poorest county in the state, is near the Mexican border, and has an 80-percent Hispanic population.[27,28] The vast majority of the patients attending the clinic were Spanish speaking only, with a long history of poor adherence with treatment.


The LAIA clinic was started in November of 2004 due to the high rates of hospitalizations reported from two out of three adult outpatient clinics of Imperial County Behavioral Health Services. Each adult clinic serves approximately 350 patients. Poor adherence with antipsychotic treatment was often recognized as a contributing factor to the high hospitalization rates. The LAIA clinic was established in the hopes it would improve adherence with treatment and, thereby, reduce hospitalizations. Treating psychiatrists referred patients with histories of poor adherence (e.g., poor attendance to outpatient appointments and/or poor adherence to medication associated with exacerbation of symptoms) to this clinic. The patients continued receiving medication management with their regular psychiatrists in addition to their participation in the LAIA clinic. The patients attended the clinic twice a week. The clinic was headed by a registered nurse and supervised by one of the authors (AC). If the patient’s request for being on RLAI was denied, he or she was started on fluphenazine decanoate. Patients started on fluphenazine were not included in this report. The main reason why patients were not started on RLAI was their lack of Medicaid coverage. Patients who missed an appointment received a phone call and a letter from the clinic, and, if applicable, the assigned case manager contacted them and had them come to soonest available appointment. The waiting period for patients to be started on RLAI was 2 to 3 weeks. By the time this cohort was started, none of the patients were on any depo antipsychotics for the last year, yet some had histories of receiving depo antipsychotics in the past.

By the end of December of 2006, we had a total of 55 patients enrolled in the LAIA clinic; 50 on RLAI and five on another depo antipsychotic, mainly fluphenazine decanoate. We decided to review the adherence of the 50 patients receiving RLAI from January 1, 2005, until December 31, 2006. The 50 patients were divided in those who had received the injection for one year and six, three, and one month. Our main outcome variable was the rate of no-show appointments to the RLAI clinic before and after being exposed to RLAI for at least one year and six and three months. Additionally, we looked at the global assessment of functioning (GAF) score when the patients entered the RLAI and at the end of the corresponding one year and six and three months of receiving RLAI.

During their appointments for the injection, the nurse recorded the patient’s weight, vital signs, presenting symptoms, level of functioning, adherence with treatment, side effects, and level of satisfaction with the LAIA. The nurse also provided support, education, and encouragement to continue attending the clinic or a biweekly basis. The following information was also reviewed and extracted from each chart by the leading author: gender, age, ethnicity, vocational status, year of enrollment in the county’s behavioral health system, current living situation, support network, use of case management, and means of transportation to the clinic. We also looked at the comorbid use, type of addictive substance, length of sobriety reported by the patient, the date of their last hospitalization, if any, and the use of other psychotropics by the time of the chart review.

Data were statistically analyzed and described using the computer software SPSS (SPSS Inc., Chicago, Illinois). Descriptive statistics were used to illustrate the distribution of the different variables. For GAF and weight variations pre-RLAI and post-RLAI, one-way t-test analysis was used. This retrospective chart review was approved by the UCSD Human Research Protection Program and the Administration of Imperial County Behavioral Health.


TABLE 1 describes the demographics of the patients included in this chart review. Among the 50 charts reviewed, 34 belonged to male patients and 16 belonged to female patients. The mean age was 38 years, the range was 18 to 63 years by the end of the chart review period in December, 2006. Seventy-four percent (74%) of the patients were Hispanics and 26 percent were non-Hispanics, mainly Caucasians. Twenty percent of the patients were married and 14 percent reported having children.

The majority of the patients (94%) were receiving government-sponsored disability. It was also found that 32 percent of the patients had never worked and almost 12 percent had not worked in the past 10 years. Most of the patients (54%) had an active case manager during the chart review period. In terms of their living situation, 62 percent lived with a parent or relative, 20 percent lived alone, 12 percent lived with their spouses, and six percent lived in a board and care facility. Forty-eight percent of patients arrived to our clinic by their own means, 36 percent were brought by a parent or relative, and 16 percent were provided with transportation by the county’s behavioral health department.

The most common diagnosis in this group was schizophrenia, paranoid type (38%), followed by schizoaffective disorder (22%) and schizophrenia undifferentiated type (14%). Twenty percent were diagnosed with a mood disorder; among those, 12 percent were diagnosed as bipolar I, four percent with a mood disorder not otherwise specified, two percent with bipolar II, and two percent were diagnosed with major depressive disorder with psychotic features.

One patient was diagnosed with conduct disorder and responded well to long-acting risperidone. According to our review, 12 patients (24%) had never been hospitalized. Nine patients (18%) were hospitalized in 2006 before starting RLAI, seven patients (14%) were hospitalized in 2005 before starting RLAI, and six patients (12%) were last hospitalized in 2004. The rest were hospitalized before 2003. The most remote hospitalization occurred in 1976. TABLE 2 summarizes the initial and last documented dose of RLAI. The majority of patients were taking other types of psychotropics while enrolled in the RLAI. TABLE 3 summarizes the other psychotropics that the 50 patients were taking in addition to receiving RLAI.

Comorbid substance use, defined as actively using addictive substances reported by patients or who were enrolled in a rehabilitation program, was found in 58 percent of patients. Methamphetamine was the most common abuse substance (34%), followed by alcohol (22%) and cannabinoids (2%). Less than six months of sobriety was reported by 28 percent of patients in this sample. Four percent had been sober for more than six months but less than one year. Twenty-six percent (26%) had been abstinent from addictive substances for more than one year. This was not confirmed objectively and was only based on patient report.

Among the 50 patients reviewed, 34 (68%) received RLAI for at least one year, seven (14%) for at least six months, seven (14%) for at least three months, and two patients (4%) received treatment with RLAI for at least one month. The rate of no-show appointments was examined pre- and post-RLAI in those patients receiving treatment for one year and six and three months. Our data showed a decrease in the no-show rate of appointments for the three different groups. For those receiving RLAI for at least one year, their no show rate decrease from 27 percent to 15 percent. For those receiving RLAI for at least six months, the rate of not show improved from 27 percent to 16 percent; and for those receiving RLAI for at least three months, the rate of no show improved from 21 percent to 17 percent. TABLE 4 summarizes these findings.

There was a significant improvement in the GAF score for those patients receiving RLAI for one year. Their GAF improved from a mean of 40.8 to 57.2 (SD=12.39, df=33, p<0.01). Similar improvement was found in those receiving RLAI for six months (mean GAF improvement from 36.4 to 51.8 [SD=9.7, df=6, p<0.01]) and three months (mean GAF improvement from 40.7 to 60.4 [SD=13.8, df=6, p<0.01]). TABLE 5 summarizes these findings.

In terms of their weight, it was noted that in patients receiving RLAI for at least one year their mean weight increased from 205.3 pounds to 211.4 pounds. Similar findings were observed in those receiving RLAI for at least six months, with a mean increase of 184.4 to 185.2 pounds. For those patients receiving RLAI for at least three months their weight decreased from a mean of 192 to 190 pounds. These results are only observational since patients were receiving other psychotropics in addition to the RLAI. It is not possible to draw any conclusions regarding the association of weight changes and use of RLAI.


Recent reports have demonstrated the improvement in adherence and remission of symptoms among patients taking RLAI for more than one year.[29] A recent prospective, two-year, follow-up study showed that RLAI is also effective in patients with bipolar disorder with a predominant depressive course with a history of poor adherence to oral psychotropics.[30] To our knowledge, there have been few studies looking at improvement in adherence among patients, mainly Hispanics, living in rural areas close to the Mexican border. Despite of the majority of these patients having a long history of poor adherence, this retrospective study shows that their rate of adherence to scheduled appointments and the global functioning improved with the administration of long-acting risperidone. The rate of hospitalization in our cohort is low considering their history of poor adherence. Factors that could explain these issues are family support and involvement of case management, which need to be corroborated with future studies. Another finding was that only eight percent of patients were solely on RLAI. Oral risperidone was reported as the most frequent concurrent antipsychotic followed by quetiapine. Future studies should assess if there is a need for concomitant use of oral psychotropics with RLAI in order to reduce symptoms, maintain adherence, and improve function.

A remarkable finding is the increased use of stimulants, mainly methamphetamines, among our patients. It was not documented if the psychotic symptoms preceded the use of these stimulants. Since the use of addictive substances was not objectively recorded, i.e., urine toxicology screen, it is not possible to draw any conclusion regarding the effect that RLAI has on the comorbid use of methamphetamines. Future studies are needed to address the effect of depo antipsychotics, intense case management, and improvement of functioning in patients with comorbid psychiatric and methamphetamine abuse.
As a pilot study, this report has several limitations. This is a preliminary retrospective study with 50 patients enrolled. Additionally, there were no objective measures of changes in their positive or negative symptoms. Most of the observations were qualitatively based on the treating psychiatrist’s observation. Additionally, the rating of the GAF was not done by blinded raters. A factor that should be considered is the possible observer bias in giving the GAF score. Moreover, there is no comparison group to determine the direct effect of the treatment received.


This report describes the outcome of a group of chronically mentally ill patients, mainly Hispanics, with a history of poor medication adherence and the success in their participation in a LAIA clinic. The results revealed generally high patient adherence with such a program and meaningful improvements in attendance to their appointments as well as functioning measured by GAF score. Because RLAI was administered in the context of a clinic in which adherence was closely monitored and that had a systematic remediation process for non-adherence (i.e., missed appointments), it is not possible to know how much of the improvements noted are attributable to treatment with RLAI specifically, participation in the clinic alone, or a combination of both. Nevertheless, this report demonstrates the utility and effectiveness of such an approach.

Our preliminary data support the need for pursuing a longitudinal observational study to determine if the improvement in patient level of functioning and use of addictive substances remains over time. There is more to learn about the natural course of schizophrenia and bipolar disorders among this cohort of patients living in this rural border region. Future studies will look at the different in doses required by Hispanics compared to other ethnic groups, since it has been reported that Hispanics need lower doses of antipsychotics31 to control their functioning. Objective measures should be obtained in order to tailor adequate psychosocial interventions to improve their ability to function in society and improve their vocational status, reduce hospitalizations, and maintain significant improvement in their adherence to treatment.


The authors want to extend their appreciation to the Administration and Staff of Imperial County Behavioral Health for their support and collaboration in the development of this project.

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