by Robert A. Lasser, MD, MBA; Nina R. Schooler, PhD; Mary Kujawa, MD, PhD;
Kathleen Jarboe, PHMCNS-BC; John Docherty, MD; and Peter Weiden, MD
Dr. Lasser is with Shire Pharmaceuticals (Dr. Lasser was with Johnson & Johnson at the time of the development of this manuscript); Dr. Schooler is with SUNY Downstate Medical Center, Brooklyn, New York; Dr. Kujawa is with Hoffman-La Roche, Nutley, New Jersey (Dr. Kujawa was with Ortho-McNeil Janssen Pharmaceutical Affairs, LLC, at the time of the development of this manuscript); K. Jarboe is with Quintiles, Inc., Atlanta, Georgia; Dr. Docherty is with Joan and Sanford I. Weill Medical College of Cornell University, New York, New York; and Dr. Weiden is with the University of Illinois, Chicago, Illinois.
Psychiatry (Edgemont) 2009;6(4):22–27
Funding for the development of this manuscript was provided by Ortho-McNeil Janssen Scientific Affairs, LLC, Titusville, New Jersey.
Dr. Lasser served as an employee of Johnson & Johnson during period of study; Dr. Schooler is a consultant for or has received educational or research grant support from AstraZeneca, Bristol-Myers Squibb, Eli Lilly & Company, Ortho-McNeil Janssen, and Pfizer; Dr. Kujawa served as an employee of Ortho-McNeil Janssen Scientific Affairs, LLC, during period of study; K. Jarboe is a member of the speakers bureau for Janssen Pharmaceutica and received honoraria for speaking engagements and participated in the Risperdal Consta research trials as a subinvestigator; Dr. Docherty has served on the speaker boards for AstraZeneca, Bristol-Myers Squibb, Janssen, and Sepracor and has received research grants from Bristol-Myers Squibb and Janssen; and Dr. Weiden is a consultant for and has received honoraria from AstraZeneca, Bristol-Myers Squibb/Otsuka American Pharmaceutical, Ortho-McNeil Janssen, Organon, Pfizer, Shire, Vanda, and Wyeth and has received grants/research support from AstraZeneca, Bristol-Myers Squibb/Otsuka America Pharmaceutical, Ortho-McNeil Janssen, and a family member has consulted for Pfizer.
Nonadherence to antipsychotic medications in serious, persistent mental illness remains a significant clinical challenge. Long-acting therapy was developed to help improve adherence to schizophrenia therapy and provide an effective means for ameliorating symptoms and preventing relapse. The Agency for Health Care Policy and Research/National Institute of Mental Health Schizophrenia Patient Outcomes Research Team recommends that antipsychotic long-acting therapy be strongly considered for patients who have difficulty adhering to an oral medication regimen or who prefer long-acting therapy. Depot conventional formulations have long been available; for clinicians and patients who would rather use an atypical antipsychotic, studies with risperidone long-acting therapy suggest that it is efficacious and well tolerated. A common concern of clinicians who elect to initiate long-acting therapy is how to introduce the possibility of changing from the current oral antipsychotic to an long-acting therapy injection. As with other aspects of patient care, having an established therapeutic relationship with the patient is advantageous for recommending changes in care, but the way in which the idea is approached may improve the likelihood of its acceptance. To help clinicians broach a recommendation of long-acting therapy with their patients, the GAIN approach was designed as a standard interview process for presenting this option. It encompasses (and is an acronym for) goal setting, action planning, initiating treatment, and nurturing motivation. This novel clinical tool is based on the principles of motivational enhancement therapy, a patient-centered approach that seeks to evoke the patient’s own motivation for change, to consolidate the decision to change, and to plan for change. This tool is also based on the Listen-Empathize-Agree-Partner, or LEAP, communication strategy. Motivational enhancement therapy, which is typically brief, has been found effective in several chronic illnesses in both outpatient and inpatient settings. GAIN may be a practical tool for aligning clinician-patient expectations and enhancing long-term maintenance of therapy.
schizophrenia, long-acting, antipsychotics, psychosocial, interview, LEAP, GAIN
Nonadherence to oral antipsychotic medications is one of the most significant clinical challenges in the treatment of schizophrenia. Reviews indicate that nonadherence rates are as high as 50 percent in the first year of treatment, and almost 75 percebnt in the first two years of treatment.[1,2]
Despite evidence that continuous antipsychotic treatment is more effective than interrupted treatment,[3,4] and the fact that long-acting therapy (LAT) is strongly recommended, LAT use in the United States remains low. Concern with this low rate of LAT use has been heightened by recent studies demonstrating that partial adherence to a prescribed medication regimen is common among patients with schizophrenia and detrimental to treatment outcomes. In an effectiveness study gauging the clinical experience of antipsychotic treatment in a naturalistic setting, Docherty et al found that 9 of 10 patients taking oral antipsychotic medication for one year were only partially adherent. The degree of their adherence was linked to outcome; lower adherence was significantly associated with higher (worse) symptom ratings. Another analysis found that patients who stopped taking their medication for as little as 10 days incurred a significantly increased risk of hospitalization. Other studies have demonstrated a direct relationship between reduced adherence, rehospitalization, and hospitalization costs.[8,9]
LONG-ACTING INJECTABLE ATYPICAL ANTIPSYCHOTICS: WHAT HAVE WE LEARNED SO FAR?
Until recently, the only LAT options in the United States were formulations of the conventional antipsychotics haloperidol and fluphenazine (i.e., haloperidol decanoate and fluphenazine decanoate). A newer alternative is currently available with an atypical antipsychotic, risperidone long-acting therapy (RLAT). Initial studies in clinically stable patients with schizophrenia or schizoaffective disorder have established the safety and efficacy of RLAT.[10–20] demonstrating significant improvements in overall symptoms and quality of life, low rates of relapse and rehospitalization and high patient satisfaction with treatment.[10,13,14,16,21] Of note, these short- and long-term studies found that RLAT was well tolerated, with low rates of discontinuation due to adverse events and reportedly little pain from injections.[10,13–16]
In addition, RLAT has been shown to be efficacious and well tolerated in elderly patients, in those with illness diagnosed within three years, and in newly diagnosed patients.[17,18] RLAT has also been evaluated in a prospective naturalistic study in patients with psychotic disorders and poor antipsychotic adherence, tolerability problems, or lack of effectiveness. Even in this difficult-to-treat population, approximately 50 percent completed the six-month study, with two-thirds of patients experiencing improvement in Clinical Global Impression (CGI) score.[19,20] Taken together, these studies suggest that RLAT provides clinical benefits for a range of patients extending beyond those who are persistently nonadherent.
RATIONALE FOR THE GAIN APPROACH
Although antipsychotic LAT has advantages over daily oral formulations, injectable medications have been reserved for only the most refractory cases of recurrent nonadherence and relapse. Use of LAT has also been limited by reluctance of many psychiatrists to administer injectable medications, confusing reimbursement procedures, and the belief that patients would invariably reject an offer of this treatment modality.[22,23]
In the relatively near future, as many as four new atypical antipsychotic LAT formulations may become available. To utilize these new therapeutic options effectively, however, several barriers associated with their use must be addressed. One of these barriers, patient acceptance, may be overcome by the use of structured psychosocial interventions. We have, therefore, developed a structured approach for gaining patient acceptance of treatment and to address the need for increased comfort on the part of clinicians in discussing LAT with patients with this goal in mind. Our approach encompasses goal setting, action planning, initiating treatment and nurturing motivation (GAIN).
DEVELOPMENT OF THE GAIN APPROACH
GAIN was developed in the absence of a structured approach for engaging patients in discussions of LAT and tested to support treatment initiation and maintenance. Motivational enhancement therapy (MET), which has been successful in motivating change in patients with alcohol and/or substance dependence,24,25 served as the platform for the GAIN approach. GAIN is based in particular on the LEAP (Listen-Empathize-Agree-Partner) communication strategy.[26,27]
LEAP focuses first and foremost on strengthening the therapeutic alliance so that the therapist/prescriber is more trusted and ultimately more persuasive in his or her recommendations to patients. LEAP was recently found to improve insight into illness, positive attitudes about treatment, adherence with long-acting injectable medication, and motivation to change in patients with schizophrenia.
As a MET-based instrument, GAIN is a structured clinical discussion tool to support clinicians and patients in considering LAT and to maintain patients’ motivation to continue treatment. This tool also addresses barriers, such as needle phobia, stigma associated with injectable antipsychotics, and concerns about adverse effects (Table 1).[10,13,14,16,21,26]
The GAIN approach was developed via collaborative consensus by an eight-member steering committee of psychiatrists, psychologists, and nurses (see Acknowledgments) and designed for implementation with relative ease by any member of a clinical treatment team during a single or multiple clinical visit(s). As a patient-centered approach, GAIN focuses on engagement with patients to optimize the opportunity for success. Table 2 includes examples of the clinical strategies that may be useful to clinicians who implement GAIN.
INITIAL APPLICATIONS OF THE GAIN APPROACH
The Schizophrenia Treatment Acceptance Response Trial (START) evaluated the effectiveness of GAIN versus approach as usual (AAU) in acceptance of RLAT at clinical centers randomized to implement either option. The study consisted of a six-week “approach” phase, during which patients were exposed to GAIN or AAU over three visits, and a 12-week “treatment” phase, during which patients received RLAT every two weeks. Rates of patient acceptance and adherence to treatment were high (and indistinguishable) in the GAIN and AAU sites. Possible reasons for these high rates include the positive effects of more frequent contact between patients and their treatment teams in this study than is typical in clinical practice, or because clinicians who participated in the trial were already motivated to encourage patients to accept LAT. Nonetheless, clinicians who used GAIN found it easy to implement, and almost all indicated that they would use this tool with their current and future patients (Janssen, data on file).
START represents the first application of the GAIN approach, and the results suggest that it may be helpful in patient care. Further evaluation of its efficacy in a clinical setting is recommended to determine whether GAIN might also be useful for other pharmacologic approaches. Indeed, with adaptation, GAIN could be valuable for all patients with schizophrenia in the quest to enhance their acceptance of and adherence to antipsychotic therapy in general. The ultimate goal is to help the individual patient achieve the full benefits of therapy by encouraging adherence to treatment as prescribed.
Clinicians can utilize GAIN for enhancing patient acceptance of and adherence to LAT by changing patients’ perception of LAT as a punitive measure to that of a team-based action for long-term success. This structured approach also may be helpful for expanding the benefits of LAT to patients other than those in the START study, who were at high likelihood of acceptance before this intervention. Our stepwise approach of discussing possible actions to reach therapeutic goals and then working collaboratively with patients to achieve those self-defined goals provides a team-based action for long-term success.
In addition to the authors, Xavier Amador, PhD, Kimberly Littrell, RN, and Alexander Miller, MD, served on the Steering Committee. George M. Garibaldi, MD, Lian Mao, PhD, and Ramy Mahmoud, MD, MPH, also provided valuable input.
The authors also wish to acknowledge the writing and editing assistance provided by Mariana Ovnic, PhD, and Helix Medical Communications (funding provided by Ortho-McNeil Janssen Scientific Affairs, LLC, Titusville, New Jersey, USA) in the development and submission of this manuscript.
1. Corrigan PW, Liberman RP, Engel JD. From noncompliance to collaboration in the treatment of schizophrenia. Hosp Community Psychiatry. 1990;41:1203–1211.
2. Perkins DO. Predictors of noncompliance in patients with schizophrenia. J Clin Psychiatry. 2002;63:1121–1128.
3. Kane JM. Schizophrenia. N Engl J Med. 1996;334:34–41.
4. Ayuso-Gutierrez JL, del Rio Vega JM. Factors influencing relapse in the long-term course of schizophrenia. Schizophr Res. 1997;28:199–206.
5. Lehman AF, Steinwachs DM. Translating research into practice: the Schizophrenia Patient Outcomes Research Team (PORT) treatment recommendations. Schizophr Bull. 1998;24:1–10.
6. Docherty JP, Grogg AL, Kozman C, Lasser R. Antipsychotic maintenance in schizophrenia: partial compliance and clinical outcome. Presented at: The American College of Neuropsychopharmacology 41st Annual Meeting. 2002 December 8-12; San Juan, Puerto Rico.
7. Weiden PJ, Kozma C, Grogg A, Locklear J. Partial compliance and risk of rehospitalization among California Medicaid patients with schizophrenia. Psychiatr Serv. 2004;55:886–891.
8. Gilmer TP, Dolder CR, Folsom DP, et al. Antipsychotic polypharmacy trends among Medicaid beneficiaries with schizophrenia in San Diego County, 1999–2004. Psychiatr Serv. 2007;58:1007–1010.
9. Valenstein M, Copeland LA, Blow FC, et al. Pharmacy data identify poorly adherent patients with schizophrenia at increased risk for admission. Med Care. 2002;40:630–639.
10. Kane JM, Eerdekens M, Lindenmayer JP, et al. Long-acting injectable risperidone: efficacy and safety of the first long-acting atypical antipsychotic. Am J Psychiatry. 2003;160:1125–1132.
11. Nasrallah HA, Duchesne I, Mehnert A, et al. Health-related quality of life in patients with schizophrenia during treatment with long-acting, injectable risperidone. J Clin Psychiatry. 2004;65:531–536.
12. Lindenmayer JP, Jarboe K, Bossie CA, et al. Minimal injection site pain and high patient satisfaction during treatment with long-acting risperidone. Int Clin Psychopharmacol. 2005;20:213–221.
13. Lasser R, Bossie CA, Gharabawi G, et al. Efficacy and safety of long-acting risperidone in stable patients with schizoaffective disorder. J Affect Disord. 2004;83:263–275.
14. Fleischhacker WW, Eerdekens M, Karcher K, et al. Treatment of schizophrenia with long-acting injectable risperidone: a 12-month open-label trial of the first long-acting second-generation antipsychotic. J Clin Psychiatry. 2003;64:1250–1257.
15. Lasser RA, Bossie CA, Zhu Y, et al. Efficacy and safety of long-acting risperidone in elderly patients with schizophrenia and schizoaffective disorder. Int J Geriatr Psychiatry. 2004;19:898–905.
16. Simpson GM, Mahmoud RA, Lasser RA, et al. A 1-year double-blind study of 2 doses of long-acting risperidone in stable patients with schizophrenia or schizoaffective disorder. J Clin Psychiatry. 2006;67:1194–1203.
17. Emsley R, Medori R, Koen L, et al. Long-acting injectable risperidone in the treatment of subjects with recent-onset psychosis: a preliminary study. J Clin Psychopharmacol. 2008;28:210–213.
18. Parellada E, Andrezina R, Milanova V, et al. Patients in the early phases of schizophrenia and schizoaffective disorders effectively treated with risperidone long-acting injectable. J Psychopharmacol. 2005;19:5–14.
19. Taylor DM, Young C, Patel MX. Prospective 6-month follow-up of patients prescribed risperidone long-acting injection: factors predicting favourable outcome. Int J Neuropsychopharmacol. 2006;9:685–694.
20. Taylor DM, Young CL, Mace S, Patel MX. Early clinical experience with risperidone long-acting injection: a prospective, 6-month follow-up of 100 patients. J Clin Psychiatry. 2004;65:1076–1083.
21. Lindenmayer JP, Eerdekens E, Berry SA, Eerdekens M. Safety and efficacy of long-acting risperidone in schizophrenia: a 12-week, multicenter, open-label study in stable patients switched from typical and atypical oral antipsychotics. J Clin Psychiatry. 2004;65:1084–1089.
22. Velligan DI, Wang M, Diamond P, et al. Relationships among subjective and objective measures of adherence to oral antipsychotic medications. Psychiatr Serv. 2007;58:1187–1192.
23. Glazer WM, Kane JM. Depot neuroleptic therapy: an underutilized treatment option. J Clin Psychiatry. 1992;53:426–433.
24. Miller WR. Motivational interviewing: research, practice, and puzzles. Addict Behav. 1996;21:835–842.
25. Rubak S, Sandbaek A, Lauritzen T, Christensen B. Motivational interviewing: a systematic review and meta-analysis. Br J Gen Pract. 2005;55:305–312.
26. Amador X. I Am Not Sick, I Don’t Need Help! How to Help Someone with Mental Illness Accept Treatment t, Second Edition. Peconic (New York): Vida Press, 2006.
27. Paillot C, Goetz R, Amador, X. Double-blind, randomized, controlled study of a psychotherapy designed to improve motivation for change, insight into schizophrenia and adherence to medication. Schizophren Bull. 2009;35(1):343.