Adherence Key to Effective Management of Schizophrenia

Ms. Terrie is a clinical pharmacywriter based in Haymarket, Virginia.

Schizophrenia is a chronic, complex,and challenging disorderthat requires long-term treatment,affecting approximately 1% of theworld population—an estimated 2.5 millionindividuals in the United States—andrates of incidence are comparable amongboth men and women.^1-4 In men, theonset of schizophrenia is typically duringthe teen years or early 20s; and inwomen,the onset is typically in the 20s orearly 30s. Onset in childhood is rare; however,early adolescent or late-life onset(referred to as paraphrenia) may occur.¹

Alcohol abuse, drug abuse, social anxiety,and depression are common amongpatients with schizophrenia, and an estimated10% of schizophrenic patientscommit suicide.^4-6 Addiction to nicotine isthe most common form of substanceabuse in patients with schizophrenia; thispopulation is addicted at 3 times the rateof the general population.⁴

Schizophrenia may exist alone or inconjunction with other psychiatric ormedical conditions. In order to effectivelycounsel patients affected by schizophrenia,pharmacists should have someinsight into this condition and the treatmentoptions available for the managementof schizophrenia.

Types of Schizophrenia

Schizophrenia is categorized in the following5 subtypes:

• Paranoid schizophrenia—delusionalthoughts or auditory hallucinations,argumentativeness, and anger
• Catatonic schizophrenia—stupor, agitation,decreased sensitivity to painfulstimulus, and inability to take care ofpersonal needs
• Disorganized schizophrenia—incoherence,regressive behavior, flat effect,social withdrawal, and repetitive mannerisms
• Undifferentiated schizophrenia—symptomsof >1 type of schizophrenia
• Residual schizophrenia—more prominentsymptoms, followed by a prolongedperiod of mild negative symptoms^1-4

Causes

According to the American PsychiatricAssociation (APA), although the exactcause of schizophrenia is unknown,research suggests that biological andenvironmental factors play a role in boththe onset and course of schizophrenia.⁷In addition, scientists know that somehereditary basis or genetic predispositionfor the disease exists.^1,4,6,7 Statisticsindicate that, although an estimated 1%of the population has schizophrenia, it isseen in 10% of individuals that have afirst-degree relative with schizophrenia.⁴

Signs and Symptoms

Since no one symptom positively identifiesschizophrenia, patients may exhibitvarious types and degrees of symptoms,which can be classified into 3 generalcategories: positive symptoms (eg, delusions,hallucinations, unusual perceptionsor thoughts), negative symptoms(eg, loss or decrease in ability to initiateplans, speak, or express emotion), andcognitive symptoms (problems withattention, sustaining attention, certaintype of memory, and ability to plan andorganize things).^1,2,4,6,7

Effective Patient Counseling

Because schizophrenia is a long-termand recurrent illness, patient adherenceto therapy is essential. At the annual APAmeeting in May 2007, results were presentedfrom the National AdherenceInitiative in Schizophrenia Survey, whichinvolved 13,000 patients with schizophreniaand used a new screening tool.The survey indicated that the most commonreasons for failing to take medicationprescribed for schizophrenia by 2out of 3 patients included poor insight(74%), forgetting to take medication(68%), and previous discontinuation ofmedication (67%).⁶ The screening toolidentified 8 factors that can be associatedwith nonadherence: (1) poor insightabout illness; (2) forgetting medication;(3) stigma associated with taking medication;(4) presence of psychotic symptoms;(5) previous discontinuation ofmedication; (6) stigma about hospitalization;(7) drug/alcohol abuse; and (8) experiencingadverse effects from prescribedmedication.⁸

Treatment

Although no cure exists for schizophrenia,a variety of treatment optionsare available for its management, includingpharmacologic therapy, psychotherapy,rehabilitation, and family and communitysupport.^1,2,4 The main goals oftherapy are the reduction or exacerbationof symptoms and to minimize theincidence of relapse.⁵ An early diagnosisand initiation of a treatment plan are veryimportant and may prevent or delay theseverity of this condition or the need toconsider augmentation therapy.^5,9

The 2 general classes of drugs availablefor treating this condition are conventionalantipsychotics (eg, chlorpromazine[Thorzine], thioridazine [Mellaril],and haloperidol [Haldol]) and atypicalantipsychotics (eg, clozapine [Clozaril],risperidone [Risperdal], olanzapine [Zyprexa],quetiapine [Seroquel], ziprasidone[Geodon], and aripiprazole [Abilify]),which are available in a variety of dosageforms, such as tablets, oral-disintegratingtablets, liquids, and short- and long-actingintramuscular injections. Switching tothe use of injectable long-acting antipsychoticsvia intramuscular administrationfor certain patients (ie, patients withindifference or denial of illness who cannotreliably take daily oral medications)may be necessary and also may producebetter results in efficacy, tolerability, andrelapse prevention.^1,5

Conventional antipsychotics can controlpositive symptoms such as delusionsand hallucinations. Adverse effects associatedwith the use of conventionalantipsychotics include sedation, dystonia,tremors, elevated prolactin levels,and weight gain. These agents also maycause akathisia (motor restlessness),which may result in patient nonadherence,as well as tardive dyskinesia.¹

Atypical antipsychotics were firstintroduced in the 1990s and are used tomanage both positive and negativesymptoms associated with schizophrenia.These agents are less likely to causeextrapyramidal effects, may have a lowerincidence of tardive dyskinesia, and producelittle or no elevation of prolactin levels.1 According to a joint panel of theAmerican Diabetes Association, the APA,the American Association of ClinicalEndocrinologists, and the North AmericanAssociation for the Study of Obesity,the use of atypical antipsychotics is associatedwith incidence of weight gain.¹⁰Studies also show an association betweenatypical antipsychotic use and thedevelopment of prediabetes, diabetes,and elevated blood lipid levels.¹⁰

The panel recommends baselinescreening of personal and family historyof obesity, diabetes, and dyslipidemia,fasting glucose, and fasting lipid profileprior to initiating therapy and routinemonitoring while on therapy.^5,10 It alsoconcluded that the atypical antipsychoticsdiffer in their risk profiles and thatsome agents, although effective treatmentoptions, raise a greater risk ofweight gain, diabetes, and lipid disordersthan other agents.¹⁰

Clozapine and olanzapine produce thegreatest weight gain; quetiapine andrisperidone produce intermediate weightgain; ziprasidone and aripiprazole producethe least weight gain.^10,11 Resultsfrom a study published in the January 9,2008, issue of the Journal of the AmericanMedical Association report that metforminand lifestyle interventions, aloneor in combination, were effective forantipsychotic-induced weight gain andabnormalities in insulin sensitivity.^11,12

Although the FDA had not previouslyapproved any medication to treat schizophreniain adolescents, the FDA approvedrisperidone in August 2007 and approvedaripiprazole in November 2007 for thetreatment of schizophrenia in adolescentsaged 13 to 17.^13,14 Also in November 2007,quetiapine extended-release tablets receivedan expanded indication and wereFDA approved for maintenance treatmentof schizophrenia in adults.¹⁵

The Pharmacist's Role

As one of the most accessible healthcare professionals, pharmacists can positivelyimpact patient outcomes by stressingthe importance of medication adherence,as well as encouraging patients tomaintain routine visits with their primaryhealth care provider. When counselingpatients, pharmacists should remindthem about the benefits of medicationtherapy and educate them of the potentialadverse effects of the selected medication.

For more information on schizophrenia,please visit the followingWeb sites:

National Alliance on Mental Illness:

www.nami.org

National Institute of Mental Health,

National Institutes of Health:

www.nimh.nih.gov

Mental Health America (formerly

known as the National Mental

Health Association):

www.nmha.org

Patients should be reminded to not discontinueany of their medication unlessdirected by their physician, report anyside effects to their primary health careprovider, and to not use any other medications,including nonprescription drugs,vitamins, and herbal medications, withoutseeking advice from their primary healthcare provider. It also is important forpatients to be advised against the use ofalcohol. Because quitting smoking maybe difficult for patients with schizophrenia,smoking cessation strategies such asnicotine replacement methods may berecommended. If patients do not stopsmoking or start smoking, physiciansshould monitor their response to antipsychotictherapy.⁴

Successful therapy starts whenpatients have a thorough understandingof their therapy and the importance oftherapy adherence. Pharmacists can beinstrumental in identifying possible contraindicationsor drug interactions for thispatient population and recommendingvarious strategies that patients can useto increase adherence to their therapy,such as the use of medication reminderdevices, using automated-refill featuresto ensure prescriptions are filled on time,and using 1 pharmacy for all prescriptions.Most importantly, pharmacists canassist patients with schizophrenia byshowing empathy, providing encouragementand support, and reminding themthat adhering to their therapy is themost effective tool in managing schizophrenia.

References

• Beers M, Porter RS, Jones TV, et al. Psychiatric disorders. In: The Merck Manual of Diagnosis and Therapy. 18th ed. Whitehouse Station, NJ: Merck Research Laboratories. 2006:1722-1732.
• Schizophrenia: What You Need to Know. Mental Health of America Web site. www.mentalhealthamerica.net. Accessed January 2, 2008.
• Understanding Schizophrenia and Recovery. National Alliance on Mental Illness Web site. www.nami.org. Accessed January 2, 2008.
• Schizophrenia. National Institute of Mental Health Web site. www.nimh.nih.gov. Accessed January 4, 2008.
• Mahgerefteh S, Pierre JM, Wirshing DA, et al. Treatment challenges in schizophrenia: a multifaceted approach to relapse prevention. Psychiatr Times. 2006;23(4). www.psychiatrictimes.com.
• Schizophrenia. Medline Plus Web site. www.nlm.nih.gov. Accessed January 6, 2008.
• Let's Talk Facts About Schizophrenia. American Psychiatric Association Web site. healthyminds.org. Accessed January 13, 2008.
• New screening tool can help identify patients who fail to take their medication as prescribed [press release]. Titusville, NJ: Janssen LP; May 22, 2007. Janssen Pharmaceutical Web site. www.janssen.com. Accessed January 10, 2008.
• Davis J. The Choice of Drugs for Schizophrenia. New Engl J Med. February 2, 2006;354(5):518-520. content.nejm.org. Accessed January 10, 2008.
• Antipsychotic Drugs Raise Obesity, Diabetes and Heart Disease Risk. American Diabetes Association Web site. www.diabetes.org. Accessed January 10, 2008.
• Lie D. Metformin and lifestyle changes effective in antipsychotic-induced weight gain. Medscape Web site. www.medscape.com. Accessed January 11, 2008.
• Wu RR, Zhao JP, Jin H, Shao P, Fang MS, Guo XF, et al. Lifestyle intervention and metformin for treatment of antipsychotic-induced weight gain. JAMA. 2008;299(2):185-193.
• FDA Approves Risperdal for Two Psychiatric Conditions in Children and Adolescents. FDA Web site. www.fda.gov. Accessed January 10, 2008.
• U.S. Food and Drug Administration approves ABILIFY (aripiprazole) for adolescent patients with schizophrenia [press release]. Tokyo, Japan, and Princeton, NJ: Otsuka Pharmaceutical Co Ltd and Bristol-Myers Squibb Co; November 6, 2007. newsroom.bms.com.
• Seroquel XR Receives Approval From FDA For Maintenance Treatment Of Schizophrenia. Medical News Today Web site. www.medicalnewstoday.com. Accessed January 10, 2008.