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Adherence Failure in : A Forensic Review of Rates, Reasons, Treatments, and Prospects

John L. Young, MD, Reuben T. Spitz, PhD, Marc Hillbrand, PhD, and George Daneri, MSN

Forensic patients with schizophrenia who fail to adhere to prescribed antipsy- chotic medication risk recidivism, which continues to be a serious concern. It affects all stages of trial proceedings and impacts on the treaters' liability. Al- though much remains unchanged since the authors reviewed the subject in 1986, significant advances have occurred. A patient's insight can be assessed with greater precision. Risks posed by past noncompliance, substance abuse, and a dysphoric response to medication are more clearly documented. Clinical and laboratory methods for assessing compliance have improved. Major advances in the effective amelioration of adverse effects can be applied to promote adherence. New augmentation strategies enable adequate treatment at lower doses. The development of atypical agents makes compliance easier to achieve and maintain. Other advances apply to the containment of relapse when it does occur. This review organizes the literature documenting these trends for use in both treatment and consultation.

Recent advances in the treatment of schizo- with its potential for relapse and recidivism phrenia have so far not improved adherence has not changed over the 12 years since this to treatment nor have they decreased the subject was updated under a forensic codi- public's concern about the violence of some fication.' At the same - time, notable patients with this disorder. In fact, the re- progress in the understanding and treatment ported risk of medication noncompliance of schizophrenia has produced develop- ments hlghly relevant to the problems of The authors are affiliated with the Whiting Forensic Division of Connecticut Valley Hospital, Middletown, noncompliance and relapse. The purpose of CT. Drs. Young and Hillbrand are also affiliated with this update is to organize and present this the Yale University School of Medicine, New Haven, CT. Dr. Spitz is affiliated with the Albert Einstein Col- information for the use of those who treat lege of Medicine, Bronx, NY. An earlier version of this forensic patients with schizophrenia and paper was presented at the 27th annual meeting of the American Academy of Psychiatry and the Law, October, consult on the issue of potential dangerous- 1996, San Juan, PR. Address correspondence to: John L. Young, MD, Box 70, Middletown, CT 06457. E-mail ness arising from relapse following nonad- address: [email protected] herence to prescribed medication.

426 J Am Acad Psychiatry Law, Vol. 27, No. 3, 1999 Medication Adherence Failure

This review provides information that compliance rates for all of medicine con- applies to both criminal and civil pro- tinue to be approximately 50 percent; the ceedings. Medication compliance influ- usual methods for measuring compliance ences the handling of pretrial matters are interviews, pill counts, and assays such as diversion programs, bail negotia- based on the or a marker; and clini- tions, restorations of competency to stand cians persist in blaming the patient for trial, plea bargains, and applications for default. Treaters also remain poor predic- accelerated rehabilitation. After trial, tors of their own patients' default rates." medication compliance is salient to dis- The many forms of compliance failure cussions of alternatives to incarceration, continue to include the following: inade- sentence modification, parole application, quate engagement in the treatment rela- and the management of insanity acquit- tionship after accepting a referral, re- tees. Deliberations about the prospect of peated missed appointments, ignoring or noncompliance leading to dangerousness misinterpreting instructions or adjusting or grave disability dominate civil cornmit- the medication regimen independently, ment proceedings. The issue continues to and abrupt termination of treatment.'' be of concern in connection with efforts to Since failure to comply with depot (long- assure patients' rights and their informed acting injectable) is readily consent to proposed medication regimens. recognizable, noncompliance with oral Most applications for the information medications retains the primary focus. In presented here are not new. Liability for accordance with continuing concern alleged negligent release is the major ex- about undue blaming of the patient, there ~eption.~This trend is especially worr- is a growing consensus on the value of some because of the decreasing length of reformulating the usage of compliance in inpatient stays and its correlation with terms of adherence, thereby acknowledg- early relap~e,~along with significant ero- ing that compliance includes participation sion of protections from such liabilit~.~ in an alliance with shared responsibility Also new is a trend favoring prearraign- for effective collaboration. " ment diversion programs. These pro- Most authors, continuing to report grams offer courts the option of an im- medication default across a broad spec- mediate referral to treatment for patients trum, use a definition based on clinical recognized to be in relapse5 and have significance. The present review, based been shown to expedite proceeding^.^ To on targeted reading of refereed journals respond to some cases, prosecutors will supplemented by literature searches cov- need expert opinion on the prognosis for ering the years 1986 through 1997, gen- ~ompliance.~ erated a total of 34 reports.'- 12-4 Table 1 summarizes the results for oral medica- Definition and Extent of tion; 35 default measurements in 29 re- Noncompliance ports show a median default rate of 46 The basic landmarks remain un- percent, ranging from 5 to 85 percent. changed since our 1986 review: general Table 2 shows the same information for

J Am Acad Psychiatry Law, Vol. 27, No. 3, 1999 427 Table 1 Results Reoorted from Investigations of Outpatient Oral Medication Compliance % Default Reference Rate (N) Subiects Observation Period Method of Detection Casper and Regani2 Newly admitted recidivists Single point Nurse rating Fernando et a1.I3 Discharged patients Up to one year Patient interview Drake et aLi4 Rural outpatients, unstable One year Patient interview, clinician housing rating Razali and Yahyai5 Readmitted patients Two weeks Questionnaires Casperi6 Patients admitted three or more Three years Patient interview, record times within 18 months review Kashner eta/.'? Random Veterans Affairs-admitted Single point Record review patients Giron and Gomez- Discharged patients Two years Self- and relatives' reports Beneytoi8 Adams and Howeig Newly admitted patients One month Interview of patient Casperi6 Patients admitted fewer than three Three years Patient interview, record times within 18 months review Hicks2' Readmitted patients Up to one year Patient interview Frank and Psychotherapy patients Six months Patient and therapist reports; G~nderson~~ record review Smoot et Readmitted patients Single point Patient interview Kelly et Discharged veterans Available past history Record review Awad and Hogan24 Clinic outpatients Single point Therapist rating Weiden and glaze^.'^ Newly readmitted high utilizers Single point Assessment by admitting team McEvoy et Discharged prior noncompliers Four to 42 months Records, clinician interviews cO Nageotte et aL2' Readmitted patients Three years Self- and relatives' reports !!= 3 Scottish Schizophrenia First episode inpatients Five weeks Radioimmunoassay of serum v, z. Research Gro~p*~ F Jenkins et Discharged patients Nine months Record review Eckman et Outpatient study volunteers Single point Caregiver rating -I Kapur et a/.' Day hospital patients Three months Riboflavin urine marker Opler et Homeless indigent men Single point Self-report sZI P Davidhizar et Newly admitted patients Single point Record review Eckman et Outpatient study volunteers Single point Psychiatrist rating !? Table 1 z Continued p. 0 % Default % 0 Reference Rate (N) Subjects Observation Period Method of Detection 3 D B~chanan~~ 32 (19/59) Patients two years after discharge Single point Records, urine tests Q McFarland et 27 (591215) Outpatients Single point Questionnaire mailed to relatives Weiden et 26 (14153) Discharged patients One month Multiple interviews, records 32 B~chanan~~ 25 (15161) Patients one year after discharge Single point Records, urine tests o(D McEvoy et 25 (9136) Discharged prior noncompliers One month Records, clinician interviews n Drake et a1.14 23 (13/56) Rural outpatients, stable housing One year Patient interview, clinician rating Opler et 18 (18/100) Never homeless indigent men Single point Self-report 5 Sellwood and Tarrier36 17 (431256) Discharged patients Up to three years Psychiatrist interview Pablo et 15 (2311 50) Readmitted patients Single point Record review Owen et 15 (2011 30) Inpatients Two one-month Self-report, informants periods six months apart Hazel et 5 (10011,992) Clinic outpatients Single point Clinician assessment

Table 2 Results Reported from Investigations of Outpatient Depot Medication Compliance Reference Default Rate % (N) Subjects Observation Period Method of Detection Bartko et 54 (30156) Discharged patients One year Appointment record Soni et 48 (42188) Medication clinic patients Up to five years Observation Tunnicliffe et 21 (18184) Medication clinic patients One year Record review Hogarty et 17 (12170) Consecutive admissions Two years Record study Pan and Tantam44 11 (471415) Medication clinic patients One year Record review Weiden et 8 (3140) Discharged patients One month Multiple interviews, records Fernando et a1.13 0 (0112) Discharged patients Up to one year Patient interview Young, Spitz, Hillbrand, eta/. reports concerning default with depot likely by grandiosity and similar symp- medication, producing a median rate of toms that interfere with insight.40,50 A 17 percent, ranging from 0 to 54 percent. thoughtful description of insight has been prepared,51 and a practical questionnaire Factors Affecting Risk of proposed for measuring it.52 Still appear- Noncompliance ing occasionally in the compliance liter- Data reported during the past dozen ature is the negative effect of so-called years confirm the basic set of interacting high expressed ernotion;l8343 but interest risk factors for nonadherence described in in this concept has turned to its part in the our 1986 report. A recent clinically ori- overall impact of family environment on ented review organizes these risk factors relapse despite compliance.53 usefully under four headings according to Authors have identified three compli- their origins: the patient, the medication, ance hazards since our 1986 report: a the environment, and the ~linician.~'The history of previous non~om~liance,~~.~~ authors rightly place responsibility for substance abuse,12' 34' 55356 and educa- therapeutic alliance with the clinician. tion. Paradoxically, the more educated They list such patient-related risk factors patients tend to be less compliant with as symptom severity, lack of insight, and prescribed rnedi~ation.~~In addition, the substance abuse. Side effects and dosage uncertainty regarding the impact of hav- issues fall under their medication head- ing an initial unpleasant or dysphoric re- ing, and the environmental factors accrue sponse to medication has been resolved; from poor personal and material support. this unpleasant experience does add to the From a forensic point of view, some risk of later noncompliance.57*58 notable shifts in emphasis have occurred. Our 1986 update described various Recent literature strikingly supports the medication side effects in detail as lead- importance of a strong therapeutic alli- ing factors that increase the risk of non- ance in increasing the rate of compli- compliance. The intervening years have an~e.~'.46 There is also an increasing em- seen such dramatic improvements in the phasis on the power of insight for treatment of side effects that rather than improving compliance.262273 47' 48 Defini- discussing them here, we cover them tions of insight have come into clearer through direct discussions of their reme- focus. For example, one study proposes dies under the heading "Promoting Com- that insight includes three factors: a stated pliance." intention to take medication, a belief that it had been helpful, and an optimistic Measuring Compliance stance toward the future. Each of these Interviews During the last decade, factors correlated positively with compli- there have been continuing efforts to or- ance one year after discharge.33 In con- ganize what is known about factors that trast, merely acknowledging one's illness influence compliance behavior into inter- and need for medication did not correlate view schedules or other instruments that with compliance,49 and it is made less can be predictively applied in clinical sit-

430 J Am Acad Psychiatry Law, Vol. 27, No. 3, 1999 Medication Adherence Failure uations. '" 24332 These instruments tend to zine has begun to identify a therapeutic be focused on patients' perceptions of window.68 Ideally, this information elimi- how medication affects their lives. Wei- nates both inadequate and excessive doses, den and colleagues59 have developed a both of which inhibit long-term compli- brief and practical interview schedule that ance. Most studies of &loperidol levels improves considerably on previous sub- show a clear therapeutic window for this jective measures, with little additional ef- drug as fort. Another have shared the re- Advantages continue to be noted for sults of their careful thinking about how alternatives to monitoring blood levels of to combine good interviewing with pill antipsychotic medications; for example, counts to assess compliance. In this con- prolactin levels may be followed.66 One text, it should be noted that devices con- can also resort to measuring levels in tinue to be developed to mark the times alternative fluids, particularly saliva.72 and dates when a pill container has been Urine presents another alternati~e,~~ opened.9*61, 62 where uric acid has been used to monitor Blood Levels Continuing study has chl~rprothixene,~~and markers added to led to increased sophistication in the clin- the medication can be assayed.' In gen- ical application of blood levels of antipsy- eral, however, improvements in the direct chotic medications, especially to avoid monitoring of blood levels have de- toxicity and minimize needless suffering creased interest in the alternatives. from side effects.63Despite this progress, frustrating limitations remain with respect Promoting Compliance to both and patients.64 However, Dynamic Factors Explorations of the process of establishing a dose that is schizophrenic patients' beliefs and feel- therapeutic without undue adverse effects ings about illness and medication indicate and of determining the corresponding that respectful consideration from clini- blood level can, for some patients, pro- cians promotes compliance with medica- vide an ideal means to both evaluate and tion.~~.74. 75 In particular, the value of promote compliance. making certain that patients understand We select some details among recently the benefits of prescribed medication in reported progress in the application of their own terms is ~lear.'~Similarly, a antipsychotic medication blood levels be- clinician who pays specific attention to cause of their particular relevance to how the patient adjusts to becoming a monitoring compliance. Levels of per- person who takes medication for mental phenazine and one of its active metabo- illness is promoting compliance.76 A lites were successfully applied to reduce moderate but vocal consumer provides side effects while maintaining therapeutic detailed applications of this principle.77 response.65 Success has been achieved in Prescribers often overlook the demon- correlating serum levels with the clinical strated value of keeping the medication response for m~lindone~~but not for flu- regimen simple. Some patients may be phenazine.67 Similar work with trifluopera- helped by a variety of user-friendly de-

J Am Acad Psychiatry Law, Vol. 27, No. 3, 1999 431 Young, Spitz, Hillbrand, etal. vices, which have been summarized re- adverse effect that needs to be acknowl- ~entl~.~These include blister packs with edged.90 Gynecomastia and galactorrhea calendars and small medication contain- can now be readily addressed by medica- ers marked for days of the week and tion change9' or by the cautious use of divided for times of the day. br~mocriptine.~~ Treatment of Side Effects Reflecting The vexing problem of weight gain from the recent trend of advances in treatments antipsychotic medication may impair com- for adverse effects of antipsychotic med- pliance to an increased extent due to grow- ications, a comprehensive review has ap- ing social pressure toward s~irnness.~' peared, with useful attention to compli- Fortunately, significant strides have ance issues.78 Most serious of all the occurred in understanding and managing adverse effects is akathisia, an intensely this problem." 4 particular, a medication unpleasant feeling of restlessness, which change to molindone, which sometimes is both common and difficult to predict.79 causes weight loss, can be con~idered.~~,~~ Akathisia can worsen symptoms of psy- Tremor and dystonia are notorious for chosis, and treating it successfully tends discouraging adherence. Recent case re- to reduce these symptoms.80 The past ports show success in treating tremor with dozen years have brought an improved rnetap~-0101~~and with primidone.98 Dys- understanding of akathisia," including tonia, or stiffness, especially affects practical objective ways to measure younger male patients and may be either it.82, 83 The often dissatisfying results acute99 or, more rarely, chronic.loOThe when using anticholinergic agents, the usual treatment is benztropine,lO' and standard treatment, are now being sur- when it fails or cannot be used, other mounted with beta blockers,84,85 benzo- similar agents can be tried.Io2 There has dia~e~ines,'~and other agents.87 These also been some success with substituting advances should prove helpful in encour- pimo~ide'~"r ~hlor~rothixene'~~for the aging medication adherence. Further, it is offending antipsychotic. Finally, al- now recognized that akathisia can appear though the practice has lately fallen from long after antipsychotic medication has favor, in some circumstances it may be been started.88 Since akathisia is a partic- advisable to give anticholinergics prophy- ularly disturbing experience for patients, lactically in order to promote compli- it must be recognized and skillfully pro- ance.~~~.106 Often these circumstances cessed in order to avoid a serious threat to can be identified with considerable con- compliance. fidence. lo' The impact of medications on sexual Dose Reduction The past dozen function remains an ill-defined problem, years have seen successful dose reduction but some progress has been made. Impo- studies, demonstrating that this can be an tence, loss of libido, and anorgasmia re- effective means of improving the treat- main problematic for some patients, but ment course as well as compliance.108 promising treatment possibilities are in- Most of the few relapses observed in one ~reasing.'~Priapism is a newly recognized study took place early in the course of

432 J Am Acad Psychiatry Law, Vol. 27, No. 3, 1999 Medication Adherence Failure dose reduction; most patients without a published since 1960 underscored the relapse in the first year had none in the value of tapering off slowly, over several next two.'09 An interesting study of 49 months, as a means of reducing the risk of newly diagnosed schizophrenic patients relapse.12' A more recent large quantita- found no difference in course for one year tive study demonstrated the same between patients given depot medication point.12' Increasing the dose in response and those receiving an oral medication to symptom emergence significantly re- only once a week."' Careful studies have duced the risk of relapse.'22 But the ex- increased the precision with which the treme of restricting medication entirely to appropriate candidates for dosage reduc- periods of symptom exacerbation (some- tion are identified. ' l2 For example, times called "targeting") was usually in- traditional predictors of good outcome ferior to continuous medication adminis- (including benign premorbid history and tration.I2' ability to acquire skills) correlated with Depot Medication Significant ad- long, relapse-free periods on no medica- vances have taken place recently in the tion.'13 One large studylI4 suggested the use of depot administration of antipsy- dose of antipsychotic medication required chotic medication, most notably the intro- for effective treatment could be used to duction of decanoate. A re- identify patients likely to relapse follow- cent five-year study'24 shows that ing withdrawal of the medication. An- haloperidol has fewer side effects and a other report1Is summarized studies illus- lower relapse rate than other neuroleptics. trating that handwriting tests instead of Nonetheless, depot remain plasma drug levels may be used to iden- underutili~ed.'~~A European source'26 tify individual patients' minimum effec- laments the apparent trend of marketing tive doses. forces away from the development of new Caution is in order when contemplating depot formulations and the promotion of this strategy. What we know about re- existing ones. Depot medication remains lapse despite compliance serves as a re- a uniquely powerful tool for compliance minder that low doses are not appropriate promotion, because when it fails the alert for all patient^."^ A British consensus clinician always knows. statement detailing guidelines for safe Great care must be taken in order to and effective use of high dose antipsy- utilize the depot route of administration. chotic medication is useful for identifying It is important to be mindful that half-life and treating patients for whom low dose is measured in months, requiring a long strategies are not appropriate."' A study period to reach steady-state concentra- quoted in the previous review' Is showing tion.I2' Therefore, a loading strategy, ei- no difference between two doses in a year ther oral or intramuscular, is often used was extended. and regrettably in the sec- for beginning depot injections,1283129 and ond year patients on the lower dose fared changes of depot dose must be very grad- much worse.'19 A review of 66 studies of ual. 130, I3 1 There is general agreement withdrawal of antipsychotic medication that the goal of finding the lowest effec-

J Am Acad Psychiatry Law, Vol. 27, No. 3, 1999 433 Young, Spitz, Hillbrand, eta/.

tive dose applies to depot medications to date include , , and that plasma levels are helpful in this and , are especially notable for detenninati~n.'~~Injection site reactions their favorable side effect profiles. Full have been reported; these reactions can details are beyond the scope of this paper, sometimes be helped by using a lower except to note an early description of concentration of drug for the injection use with forensic patients,""' and by exercising care in the injection two recent forensic trials of risperi- technique.133 Finally, the depot route of done,145,146 one study each on olanzap- administration alone is not sufficient to and quetiapine,I4' and a recent maintain compliance over extended peri- comprehensive review describing how ods of time; careful monitoring and sup- these agents are being used for patients portive therapy are needed to minimize who are aggressive and difficult to default leading to relapse.35 treat. '49 Augmentation The practice of add- ing a second drug to an antipsychotic has Containing Relapse begun to emerge strongly as a strategy Relapse containment requires a multi- to promote compliance by improving faceted strategy, with adherence promo- therapeutic response while potentially tion as one of its central components.16 moderating side effects. Among the more Unfortunately, schizophrenic patients familiar agents, both lithium'34 and val- may experience relapses of their illness pr~ate'~~continue to be found useful. despite their compliance with prescribed This is also true for benzodiazepines, es- medi~ation.'~~A recent literature review pecially l~raze~am'~~and alprazolam.'37 covering 66 medication discontinuation has also been suggested,'38 and studies found a relapse rate of 53 percent paradoxically, ida~oxan,'~~which has op- among study patients who were with- posite effects on neurotransmission but drawn from medication, and 16 percent presumably in different parts of the brain. for those kept on medication over an av- In addition, other agents have been found erage period of only 9.7 months.120 Sim- helpful: flu~xetine,'~~,14' and ilarly, a recent meta-analysis15' showed ~-c~closerine.'~~The search for more and twice as many schizophrenic patients re- better augmenting agents likely bears admitted to the hospital as a result of watching for continued progress. medication failure as from noncompli- New Medications The introduction ance during the first year after discharge, of the agents is a and equal readmission rates for both rea- major advance in the promotion of com- sons during the second year. However, pliance. It is well known that the first of physicians still tend to mistake noncom- these, clozapine, was approved in large pliance for medication failure and re- part because it proved effective for pa- spond by prescribing increasing doses of tients who had repeatedly relapsed de- antipsychotic medi~ati0n.l~~In contrast, spite medication compliance.'43 The alleged histories of noncompliance with other atypical antipsychotic agents, which medication taken on multiple readmis-

434 J Am Acad Psychiatry Law, Vol. 27, No. 3, 1999 Medication Adherence Failure sions may merely reflect a staff precon- cation is increased or treatment is restart- ~epti0n.I~~ ed.'63 Prodromal signs can164but usually Enhanced Monitoring The study of do not165appear to be psychotic. Accord- relapse despite medication compliance ing to one group of clinicians, schizo- over the past dozen years has demon- phrenic patients themselves can learn to strated a strong association with stressful recognize nonpsychotic changes as indi- life events such as a move or the death or cators that they are getting worse.'66 It retirement of a close re1ati~e.I~~Other remains evident that prodromal signs are patients at risk for relapse while taking unique for each patient and must be iden- their medication are those with poor re- tified individually by history, rather than mission of psychotic symptoms, particu- in general by type of change.'67 Practical larly negative symptoms such as isolation strategies are available for clinicians to and apathy, and those who develop extra- apply,'68. I"" including use of the fact that pyramidal side effects. '55 Relapse, some- family members often see the changes times involving noncompliance, may be first. I7O triggered by family conflict, especially Early Relapse Prediction Although with discouragement of expressing feel- some relapses occur without warning, ings,156,157missed therapy appoint- their proportion definitely tends to de- ment~,'~~and substance abuse.55 Regular crease over time, especially when the pa- monitoring for these situations will help tients and their clinicians are working contain relapse, since ordinarily three to well together.'22 The most successful six months elapse after stopping medica- study was that of Birchwood and col- tion before relapse occurs.'59 A small league~'~'who reported that their check- study shows that pharmacists can be ef- list, done biweekly by the patient and an fective at performing this task.I6O observer, predicted 79 percent of the re- Prodromal Signs During the past lapses with almost no false positives and dozen years much has been learned about with favorable responses when medica- how to recognize prodromal signs. These tion dosage was increased. Another indicators include changes in mood, ap- study'72showed how to predict at least 70 pearance, or behavior associated with a percent (and potentially more among pa- first episode that often herald the onset of tients known to be subject to relapse), a schizophrenic relap~e.'~'Marder and again with very few false positives, be- colleagues122 found that 50 percent of tween two and four weeks prior to de- symptom exacerbations were not pre- compensation. There have been recent ceded by a prodrome, while 53 percent of advances in the form of biologically untreated prodromal episodes did not lead based potential predictors of re- to exacerbations. Despite this discrep- lapse,'73.'74 but they are not yet suffi- ancy, intervention in response to pro- ciently practical for general use in the dromes greatly reduces the relapse containment of relapse. risk.'62 Prompt improvement is usual Environmental Support Strategies A when the dosage of antipsychotic medi- stable living situation of good quality fa-

J Am Acad Psychiatry Law, Vol. 27, No. 3, 1999 435 Young, Spitz, Hillbrand, etal. cilitates medication adherenceI4,26 and shown to promote medication compliance retards re~idivism.'~~It can be difficult to and thereby reduce relapses in schizo- apply this relationship to the forensic pa- phrenia.'. ". In fact, multifamily tient popu1atio1-1,'~~but the value of asser- groups are particularly efficacious in pro- tive community treatment for maintaining moting medication compliance.190A re- adherence and preventing relapse is well cent review'91 provides detailed informa- e~tab1ished.l~~A model for tailoring en- tion on how to structure these family- vironmental support to the needs of fo- based interventions for the best results. rensic patients has been sugge~ted.'~'In Patients' adherence to medication corre- a few jurisdictions environmental sup- lates with their recognition of encourage- port has been legally formalized under ment and support from those around Psychiatric Security Review Boards. them.26 These extensions of the criminal court deal effectively with noncompliance and Conclusion provide containment of relapse.'79, Forensic experts concerned with mini- Further, outpatient commitment has been mizing the problem of relapse among gaining acceptance as an effective way to schizophrenic patients as a result of med- buttress environmental support with legal ication noncompliance may view the past force. lX1 dozen years as a time of highly encour- Patients' knowledge about their medi- aging progress. Whereas our previous re- cations tends to be overestimated, espe- view emphasized risk factors, this one has cially among those with schiz~phrenia.'~~much more to report concerning interven- Although patients receiving a few lessons tions. It has become easier to deal effec- about medications will have no measur- tively with the legal concerns regarding able impact on compliance,'83~ a more schizophrenic patients' tendencies toward serious effort at patient education clearly medication noncompliance and subse- improves the rate of compliance.23.30 In quent relapse. Experts can now offer this vein, a voluntary program of care- more precise information about this issue. fully structured teaching for inpatients The fact that reported default rates none- significantly reduced the time they spent theless remain essentially unchanged in- in hospital during the succeeding year,'85 dicates that much challenging and inter- as did a cognitive-behavioral therapy pro- esting work remains to be done. ~1aze1-I~~ gram.''6 Group therapists have recently has gone so far as to state that we are now reported similar re~ults,''~particularly in a position to "eliminate most of the for patients with substance abuse prob- cases of schizophrenic relapse." lems."' There is evidence that patients Significant advances in the area of can learn to associate relief of their symp- medication adherence, in addition to toms with medication and that this asso- those reported here, are likely to continue. ciation results in better c~m~liance.'~ For example, a recent review has opened Finally, during the past 12 years, the the area of randomized trials of interven- use of family psychoeducation has been tions to promote medication compli-

436 J Am Acad Psychiatry Law, Vol. 27, No. 3, 1999 Medication Adherence Failure ance.lg3 The small number of rigorous References studies in several areas of medicine in- 1. Young JL, Zonana HV, Shepler L: Medica- clude two for schizophrenia. However, tion noncompliance in schizophrenia: codi- both of these studies were done in China, fication and update. Bull Am Acad Psychi- atry Law 14:105-22, 1986 where cultural differences hamper gener- 2. Miller RD, Doren DM, Van Rybroek G, et alizing the applications to western coun- al: Emerging problems for staff associated with the release of potentially dangerous fo- tries. Further progress in the scientific rensic patients. Bull Am Acad Psychiatry study of compliance can be expected. An- Law 16:309-20, 1988 other example is a guarded optimism re- 3. Appleby L, Desai PN, Luchins DJ, et al: Length of stay and recidivism in schizophre- garding long-term prognosis for some pa- nia: a study of public psychiatric hospital tients with schizophrenia deriving from patients. Am J Psychiatry 150:72-6, 1993 4. Felthous AR: Liability of treaters for injuries extended follow-up studies.'94 to others: erosion of three immunities. Bull The near future will doubtless prove as Am Acad Psychiatry Law 15: 115-25, 1987 interesting and productive as the recent 5. Steadman HJ, Moms SM, Dennis DL: The diversion of mentally ill persons from jails to past. Refinements in the subtyping of community-based services: a profile of pro- schizophrenia according to symptom pat- grams. Am J Public Health 85:1630-5, 1995 6. Exworthy T, Parrott J: Comparative evalua- terns are moving forward quickly'95 and tion of a diversion from custody scheme. J will enable experts to provide more reli- Forensic Psychiatry 8:406-16, 1997 able opinions regarding the prognosis for 7. Davis S: Factors associated with the diver- sion of mentally disordered offenders. Bull compliance. Similar gains in sophistica- Am Acad Psychiatry Law 22:389-97, 1994 tion increasingly mark the current studies 8. Kapur S, Ganguli R, Ulrich R, et al: Use of random-sequence riboflavin as a marker of of relapse and its prevention, with medi- medication compliance in chronic schizo- cation default as but one among a host of phrenics. Schizophr Res 6:49-53, 1992 interrelating factors. The challenge of ap- 9. Wright EC: Non-compliance-or how many aunts has Matilda? Lancet 342:909-13, 1993 plying an ever more vast and diverse clin- 10. Chen A: Noncompliance in community psy- ical literature to legal questions, while chiatry: a review of clinical interventions. remaining vigilant to ethical concerns, is Hosp Community Psychiatry 42:282-7, 1991 likely to increase in coming years. Mean- 1 1. Corrigan PW, Liberman RP, Engel JD: From while, we expect that this review will noncompliance to collaboration in the treat- ment of schizophrenia. Hosp Community provide significant assistance toward Psychiatry 41: 1203-1 1, 1990 making effective use of recent and current 12. Casper ES, Regan JR: Reasons for admission progress in the study of medication ad- among six profile subgroups of recidivists of inpatient services. Can J Psychiatry 38:657- herence among patients diagnosed with 61, 1993 schizophrenia. 13. Fernando MLD, Velamoor VR, Cooper AJ, et al: Some factors relating to satisfactory post-discharge community maintenance of chronic psychotic patients. Can J Psychiatry Acknowledgments 35:71-3, 1990 14. Drake RE, Wallach MA, Teague GB, et al: We gratefully acknowledge the literature search Housing instability and homelessness among assistance of Pauline A. Kruk, MS, and Stephen H. rural schizophrenic patients. Am J Psychia- Curtin, MS, of Hallock Medical Library, Connect- try 148:330-6, 1991 icut Valley Hospital, and the scholarly impetus of 15. Razali MS, Yahya H: Compliance with treat- Howard V. Zonana, MD, of Yale University. ment in schizophrenia: a drug intervention

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