PsychU TreatmentOptions WithNotes fileThe goals of schizophrenia treatment have evolved over the last several decades, from an early emphasis on controlling aggression and self-harm,

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Evidence-based guidelines recommend a number of psychosocial interventions for patients with schizophrenia. Assertive community treatment is a multidisciplinary approach using high-frequency contact and patient outreach to reduce the risk of hospitalization and homelessness. Supportive employment may help patients to gain independent employment. Skills training can help improve social interactions and independent living.Adjunctive cognitive behavioral therapy may help to reduce psychotic symptoms in patients on adequate pharmacotherapy. Cognitive remediation therapy is also considered effective intervention to help improve the lives of those who live with schizophrenia. Token economy systems use positive reinforcement principles to modify defined target behaviors, often in the context of a residential treatment environment. Other psychosocial interventions include family-based services to improve interactions with families, as well as interventions for substance use disorders or weight management if needed.Reference1. Kreyenbuhl J, et al. The schizophrenia patient outcomes research team (PORT):

updated treatment recommendations. Schizophr Bull. 2010;36:93-103.2. Kern RS, et al. Psychosocial treatments to promote functional recovery in

schizophrenia. Schizophr Bull. 2009;35(2):347-361.3. Eack SM. Cognitive remediation: A new generation of psychosocial interventions

for people with schizophrenia. Soc Work. 2012;57(3):235-246.

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Beginning in the 1950s, and continuing through several decades, deinstitutionalization resulted in transition of patients from inpatient psychiatric hospitals to the community.1 UK and US data revealed that during the transition of patients from psychiatric hospitals into “community care” there were several barriers to treatment including the discordant communication between various mental health staff within the community with little interaction between psychiatrists, psychologists, and community nurses.1 Typical antipsychotics (including phenothiazines) were fairly effective in reducing positive symptoms, enabling this deinstitutionalization.2

As early as 1965, data began to accumulate showing that medication partial or nonadherence rates for psychiatric patients averaged between 48% to 60%.3, 4 The 1960s also saw the introduction of the first atypical into clinical trials,5 as well as development of the first typical LAI,1 both of which held promise of improved adherence. Throughout the 1970s and 1980s, atypical antipsychotics became more widely available across Europe for clinical use (but only became available in the US in 1990),5 and other oral atypicals continued to be introduced through the 1990s and into the 2000s.2 In the 1990s and 2000s, they were therefore added into evidence-supported guidelines as first-line treatments of schizophrenia.6 The next major therapeutic advance occurred in 2002, with the approval of the first atypical LAI.4

References

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1. Johnson DAW. Historical perspective on antipsychotic long-acting injections. BJP. 2009;195:S7-S12.

2. Tandon R, Nasrallah HA, Keshavan MS. Schizophrenia “just the facts”: 5. Treatment and prevention past, present, and future. Schizophrenia Res. 2010;122:1-23.

3. Wilcox DRC, Gillan R, Hare EH. Do psychiatric out-patients take their drugs? BMJ. 1965;2:790-792.

4. Patel M, Taylor M, David AS. Antipsychotic long-acting injections: mind the gap. BJP. 2009;195:S1-S4.

5. Tandon R. Antipsychotics in the treatment of schizophrenia: an overview. J ClinPsychiatry. 2011;72(suppl 1):4-8.

6. McEvoy JP, Scheifler PL, Frances A. Expert Consensus Guideline series: treatment of schizophrenia 1999. J Clin Psychiatry. 1999;60(suppl 11):1-80.

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The goals of schizophrenia treatment have evolved over the last several decades, from an early emphasis on controlling aggression and self-harm, to the more recent focus on increasing quality of life and an evolving goal for remission and recovery.

ReferenceJuckel G and Morosini PL. The new approach: psychosocial functioning as a necessary outcome criterion for therapeutic success in schizophrenia. Curr OpinPsychiatry. 2008;21:630-639.

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Patients with schizophrenia in the United States between January 1, 2005, and September 30, 2010, were identified from the Truven Health MarketScan® commercial health care claims database.1 Patients included in the study were ≥13 years of age and had at least 12 months of continuous coverage before (baseline) and after (follow-up) the earliest antipsychotic usage (index event).1 Medication adherence was estimated with a medication possession ratio (MPR), which represents the time each patient possessed a drug compared with the total expected duration of therapy.1 Patients with an MPR ≥0.7 during the follow-up period were allocated to the highly adherent cohort. Those with an MPR <0.7 were assigned to the low adherence cohort.

1462 Patients with schizophrenia met the inclusion criteria: 396 (27%) were classified as adherent (“high compliance”), with a mean MPR of 0.92; 1066 (73%) were classified as having low adherence, with a mean MPR of 0.24.1

A total of 876 patients were identified from a 2007–2008 nationwide survey of adults with a self-reported diagnosis of schizophrenia currently using an antipsychotic medication.2 A total of 48% reported that they sometimes forget to take their medication, with only 43% responding ‘no’ to all 4 nonadherent behavior questions.2

However, as medication adherence was self-reported, the rate of poor adherence could not be confirmed.2

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References1. Wong B, Offord S, Mirksi D, Lin J. Characteristics associated with antipsychotic

drug adherence among schizophrenic patients in a US managed care environment. Presented at: 2012 Meeting of the American Psychiatric Association; May 5-9, 2012; Philadelphia, PA. Poster NR6-25.

2. DiBonadventura M, Gabriel S, Dupclay L, et al. A patient perspective on the impact of medication side-effects on non-adherence: results of a cross-sectional nationwide survey of patients with schizophrenia. BMC Psychiatry. 2012;12:20.

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Several factors contribute to poor adherence to medication in schizophrenia. Lack of insight is one of the most important contributors and may range from denial of the illness to lack of appreciation that medications are required to treat specific symptoms and to reduce the risk of relapse.Impairment in cognition can also interfere with the patient’s ability to properly comply with prescribed treatment regimens. In addition, psychotic symptoms (including delusions, hallucinations, and thought disorders) can interfere with a patient’s ability to adhere to treatment.Poorresponse to antipsychotics, as well as the lag time required to titrate some medications up to a therapeutic dose may result in a patient losing patience in waiting for a treatment response. Another driver of nonadherence is intolerable side effects, including weight gain, sedation, orthostasis, and akathisia. Environmental factors, including the high cost of medication and lack of a good therapeutic alliance with the treatment team can also contribute to nonadherence. In addition, comorbid substance abuse has also been demonstrated to be of significant importance in influencing adherence.

ReferenceBirnbaum M, Sharif Z. Medication adherence in schizophrenia: patient perspectives and the clinical utility of paliperidone ER. Patient Prefer Adherence. 2008;2:233-240.

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Positive aspects of certain psychosocial treatments include: beneficial effects on clinical and functional outcomes – for example, family intervention has been found to potentially reduce relapse rates;1 cognitive behavioral therapy has been found to potentially result in a reduction in positive symptoms2 and improvements in social competence.3 In an ex-US, randomized, controlled trial of 1268 patients with early-stage schizophrenia, patients were assigned to antipsychotic treatment alone or with 12 months of psychosocial intervention. Results demonstrated that the combined group showed reduction in medication discontinuation, lower risk of relapse and hospitalization, and improved quality of life. 4

There are several disadvantages to psychosocial treatment. First, progress in treatment is likely to be slow with periodic disruptions and periods of regression. Therefore, it is important that treatment be long-term, extending over months and years.5 Also, because of individual differences among patients with schizophrenia and within the same patient over time, treatment must be tailored to the needs of each patient and adjusted as the patient changes.5 Another disadvantage of psychosocial therapy is that treatment must be adapted to the patient’s illness-related cognitive impairments, such as memory, attention, and executive functioning.5

References1. Penn DL, Waldheter EJ, Perkins DO et al. Psychosocial treatment for first-

episode psychosis: a research update. Am J Psychiatry. 2005:2220-2232. 2. Guo X, Zhai J, Liu Z et al. Antipsychotic medication alone versus combined with

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psychosocial intervention on outcomes of early stage schizophrenia: a randomized, one-year study. Arch Gen Psychiatry. 2010;67:895-904.

3. Bellack AS. Psychosocial treatment in schizophrenia. Dialogues Clin Neurosci. 2001;3:136-137.

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Oral antipsychotics are frequently used in the treatment of patients with schizophrenia.1 Because they have been available for many years, generics are available for some agents (thereby decreasing the cost) and physicians have a great amount of clinical experience with them.2 In addition, there is flexibility in dosing and a short duration of action allows the physician to watch for any side effects and easily make adjustments.3

One disadvantage of oral antipsychotics is that they require daily administration.4This results in the potential for poor compliance, as the patient (often with cognitive impairment) or the family/caregiver needs to remember to take/dispense the medication daily.3 In addition, oral medications are limited by first-pass metabolism, which may result in variable absorption.3

References1. Citrome L. A systematic review of meta-analyses of the efficacy of oral atypical

antipsychotics for the treatment of adult patients with schizophrenia. Expert OpinPharmacother. 2012;13:1545-1573.

2. Albright B. Three key antipsychotics lose patent protection. Behavioral Healthcare. 2011 Nov 16. http://www.behavioral.net/article/three-key-antipsychotics-lose-patent-protection?page=2. Accessed October 2, 2013.

3. Burton N. Psychiatry. Second edition. Wiley-Blackwell, West Sussex, UK; 2010.4. NPS Data sheet 2011.

www.nps.org.au/__data/assets/pdf_file/0017/130328/NPS_Antipsychotics_DRU

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G_TABLE.pdf. Accessed October 2, 2013.

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LAIs demonstrate good adherence due to monthly, rather than daily, treatment.1 For example, in a 1-year study of Florida Medicaid patients (N=12,032), patients with schizophrenia spectrum disorders taking atypical LAIs demonstrated better adherence (72%) vs patients taking oral atypical antipsychotics (64%) (p<0.05).2LAIs are also associated with a decrease in rehospitalizations: a retrospective database analysis showed that over a mean 30-month follow-up period, atypical LAIs were associated with significantly lower mean number of rehospitalizations vs oral antipsychotics (1.25 vs 1.61; p<0.001).3 In addition, adherence is transparent, with health care professionals being alerted if the patient does not come in for treatment. Other benefits include a reliable drug delivery system with reduced peak-trough plasma levels, improvement patient outcomes and patient and physician satisfaction, lower relapse rates, and ease of administration (due to the absence of unintentional nonadherence) compared to oral agents.1,4,5

However, there are negatives associated with LAIs. These include patients’ potential concerns related to the possible pain of injections and concerns over the potential loss for autonomy and fear of being controlled.6 In addition, they are difficult to adjust with small doses and there are a limited number of formulations available.6Also, dose titration can be slow, with longer time required to reach steady state and oral antipsychotic supplementation may be necessary during this time.4 Another negative is that small amounts of drug may leak into the subcutaneous tissue, with possible irritation of the skin.4 In addition, the presence of side effects may be prolonged.4

References

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1.Patel M et al. Antipsychotic long-acting injections: mind the gap. Br J Psychiatry. 2009;195:s1-s4.

2.Lang K, Meyers JL, Korn JR, et al. Medication adherence and hospitalization among patients with schizophrenia treated with antipsychotics. Psychiatr Serv. 2010;61:1239-1247.

3.Lafeuille M-H, Laliberte-Auger F, Lefebvre P, et al. Impact of atypical long-acting injectable versus oral antipsychotics on rehospitalization rates and emergency room visits among relapsed schizophrenia patients: a retrospective database analysis. BMC Psychiatry. 2103:113:221.

4.Agid O, Foussias G, Remington G. Long-acting injectable antipsychotics in the treatment of schizophrenia: their role in relapse prevention. Expert OpinPharmacother. 2010;11:2301-2317.

5.Geerts P, Martinez G, Schreiner A. Attitudes towards the administration of long-acting antipsychotics: a survey of physicians and nurses. BMC Psychiatry. 2013;13:58.

6.Jeong H-S, Lee M-S. Long-acting injectable antipsychotics in first-episode schizophrenia. Clin Psychopharm Neurosci. 2013;11:1-6.

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Clinicians may encounter several challenges when initiating treatment with patients. This slide reviews some challenges and possible approaches a clinician can use to address those challenges.

Challenge: Patient embarrassment/shame1

Approach: Set up a modern clinical space for administration where education, support, and physical health screening can be offered.2

Challenge: Lack of insight3

Approach: Involve family members/support system.

Challenge: Cost/insurance coverage4

Approach: Refer patients to social services if needed (eg, Medicaid, Social Services Disability).

Challenge: Overburdened public agencies5

Approach: Identify a prescriber advocate within the organization and develop a program team to identify and address barriers.

Challenge: Cultural differences6

Approach: Be sensitive to cultural differences in views of mental illness and the role of treatment.

References

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1. Patel M, De Zoysa N, Bernadt M, et al. Depot and oral antipsychotics: patient preferences and attitudes are not the same thing. J Psychopharmacol. 2009;23:789-796.

2. Waddell L, Taylor M. Attitudes of patients and mental health staff to antipsychotic long-acting injections: systematic review. Br J Psychiatry. 2009;195:S43-S50.

3. Beck EM, Cavelti M, Kvrgic S, et al. Are we addressing the ‘right stuff’ to enhance adherence in schizophrenia? Understanding the role of insight and attitudes towards medication. Schizophrenia Res. 2011;132:42-49.

4. Velligan DI, Weiden PJ, Saiatovic, et al. Strategies for addressing adherence problems in patients with serious and persistent mental illness: recommendations from the expert consensus guidelines. J Psych Pract. 2010;16:306-324.

5. Velligan DI, Medellin E, Draper M, et al. Barriers to, and strategies for, starting a long acting injection clinic in a community mental health center. Community MentHealth J. 2011;47:654-659.

6. Opolka JL, Rascati KL, Brown CM, et al. Role of ethnicity in predicting antipsychotic medication adherence. Psychiatry. 2003;37:625-630.

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Clinicians initiating discussion of LAIs may be concerned about how to approach the change from an oral antipsychotic to LAI therapy. Approach to the discussion may influence patient acceptance of LAI therapy. A standardized interview is one approach that may be helpful to increase clinician comfort with the process and gain patient acceptance of LAI therapy through discussion of expectations, goal-setting, and factors for long-term treatment success.1

Motivational enhancement therapy (MET) or motivational interviewing are potential patient-centered approaches that may be helpful in chronic illness.1-3

References1.Lasser R, Schooler NR, Kujawa M, et al. A new psychosocial tool for gaining

patient understanding and acceptance of long-acting injectable antipsychotic therapy. Psychiatry. 2009;6:22-27.

2.Rubak S, Sandbaek A, Lauritzen T, Christensen B. Motivational interviewing: a systematic review and meta-analysis. Br J Gen Pract. 2005;55:305-312.

3.Rüsch N, Corrigan PW. Motivational interviewing to improve insight and treatment adherence in schizophrenia. Psychiatr Rehabil J. 2002 Summer;26(1):23-32.

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