Jonathan P. Lacro

Lower Incidence of Tardive Dyskinesia with Risperidone Compared with Haloperidol in Older Patients

OBJECTIVE: To compare the 9‐month cumulative incidence of tardive dyskinesia (TD) with risperidone to that with haloperidol in older patients.

Interventions to improve antipsychotic medication adherence: review of recent literature.

Antipsychotic nonadherence is an important barrier to the successful treatment of schizophrenia and can lead to clinical and economic burdens. Interventions capable of significantly improving medication adherence in patients with schizophrenia would be beneficial in maximizing treatment outcomes with antipsychotics. This article reviews recent literature reporting interventions designed to improve antipsychotic adherence in patients with schizophrenia. We searched the Medline, Healthstar, and PsycInfo electronic databases for articles published since 1980 on interventions to improve medication adherence in schizophrenia. Twenty-one studies met our selection criteria. In this review, educational, behavioral, affective, or a combination of these approaches to improve adherence were exammed. A total of 23 interventions were tested, as 2 studies investigated more than 1 intervention. While study design and adherence measures varied across the trials reviewed, medication adherence was noted to moderately improve with 15 of the 23 interventions tested. Interventions of a purely educational nature were the least successful at improving antipsychotic adherence. The greatest improvement in adherence was seen with interventions employing combinations of educational, behavioral, and affective strategies with which improvements in adherence were noted in 8 out of 12 studies, with additional secondary gains such as: reduced relapse, decreased hospitalization, decreased psychopathology, improved social function, gains in medication knowledge, and improved insight into the need for treatment. Longer interventions and an alliance with therapists also appeared important for successful outcomes. The continuing development and study of successful interventions to improve medication adherence are necessary to maximize the usefulness of pharmacologic treatment of schizophrenia.

Conventional vs. Newer Antipsychotics in Elderly Patients

Elderly patients with schizophrenia and dementia patients with agitation are frequently candidates for antipsychotic treatment. Conventional neuroleptics have relatively little effect on negative symptoms and may cause considerable side effects, especially in elderly patients. The authors have found a 29% cumulative annual incidence of tardive dyskinesia (TD) in middle-aged and elderly outpatients treated with relatively low doses of conventional neuroleptics Newer antipsychotics are less likely to cause extrapyramidal symptoms and may be associated with a lower risk of TD. They are generally effective for both positive and negative symptoms and may also improve some aspects of cognition, but these drugs have their own side effects. Dosing requirements for elderly patients tend to be much lower than those for younger adults.

Medication management ability assessment: results from a performance-based measure in older outpatients with schizophrenia.

Patients with schizophrenia who adhere to physicians’ recommended use of medications are less likely to relapse than those who do not. Selfreport measures of adherence have been criticized on a number of grounds. Here we describe a performance-based measure of medication management, the Medication Management Ability Assessment (MMAA), which represents a modification of the Medication Management Test used in individuals with HIV infection. Subjects were 104 patients older than 45 years with diagnoses of schizophrenia or schizoaffective disorder, and 33 normal comparison subjects (NCs). Subjects participated in a role-play task (MMAA) that simulated a prescribed medication regimen similar in complexity to one that an older person is likely to be exposed to. The total number of pills over that prescribed, total number of pills under that prescribed, and total number of correct responses were calculated. Self-report and prescription record data on adherence as well as data on measures of psychopathology, global cognitive status, and other clinical measures were also gathered. MMAA role-plays required 15 minutes, and its 1-week test–retest reliability was excellent (intraclass correlation coefficient, 0.96). Patients committed significantly more errors in medication management compared with NCs. Significantly more patients were classified as being nonadherent (i.e., taking ±5%, 10%, 15%, or 20% of prescribed pills) compared with NCs. Patients with more severe cognitive deficits performed worse on the MMAA. MMAA performance was significantly related to prescription refill records, performance-based measures of everyday functioning, and self-reported quality of life. The MMAA is a useful instrument for observing ability to manage medications in patients with schizophrenia. The measure was related to severity of cognitive impairment, suggesting that adherence may improve with psychotropic and psychosocial interventions that target these deficits.

Antipsychotic-Induced movement disorders in the elderly: epidemiology and treatment recommendations.

We reviewed the epidemiological aspects of antipsychotic-induced movement disorders as they pertain to older patients. The incidence and prevalence of drug-induced parkinsonism and tardive dyskinesia (TD) are significantly greater in the older patient than in the younger patient whereas akathisia seems to occur evenly across the age spectrum and dystonia is uncommon among older patients. The literature on risk factors associated with treatment-emergent movement disorders is highly variable. Treatment practices vary across the age range and the interaction between age and antipsychotic dosage confounds our understanding of the relative importance of treatment-related risk factors. However, there is general agreement that pre-existing extrapyramidal signs (EPS) increase the vulnerability of the patient to developing significant drug-induced movement disorders. Elderly patients with dementia are at greater risk than patients without dementia for persistent drug-induced EPS.Management of drug-induced movement disorders in the older patient requires careful consideration of the contraindications imposed by such agents as anticholinergics and β-blockers. At present, well-controlled double-blind studies of second-generation antipsychotics such as clozapine, risperidone, olanzapine or quetiapine for reducing the risk of treatment-emergent movement disorders in the elderly have not been published. However, open-label studies of atypical antipsychotics demonstrate a markedly lower incidence of both EPS and TD compared with conventional antipsychotic treatment in the elderly. There is emerging literature in support of atypical antipsychotics for the treatment of existing drug-induced movement disorders. More controversial is the use of adjunctive antioxidants in newly treated patients who are vulnerable to drug-induced movement disorders. While the evidence is mixed in support of antioxidants for the treatment of TD, the possibility remains that prophylactic use of antioxidants may help reduce the incidence of TD.The development of a drug-induced movement disorder often reduces the quality of life in an elderly patient. Effective pharmacological management requires cooperation from the patient and family, which can be fostered early in the patient’s care through proper informed consent. The risks and benefits of antipsychotic treatment in the elderly patient need to be communicated to the patient and family. At the present time, there is no consistently effective treatment for patients with TD once it develops. Therefore, attention should focus on its prevention and close monitoring.

Incidence and predictors of drug-induced parkinsonism in older psychiatric patients treated with very low doses of neuroleptics.

The available literature suggests that a sizable proportion of patients placed on neuroleptics develop acute and subacute extrapyramidal side effects, including neuroleptic-induced parkinsonism (NIP). The presence of mild, spontaneous extrapyramidal signs in the elderly makes it difficult to accurately estimate the incidence of NIP in this subgroup of patients. We examined the incidence of NIP in 56 older, newly medicated, psychiatric patients. Fifteen age-comparable, unmedicated psychiatric patients underwent 2 assessments to estimate natural fluctuation in extrapyramidal signs, and 49 normal, healthy, elderly individuals were also studied to establish age-comparable norms for the assessment of parkinsonism. Potential pretreatment predictor variables included instrumental measures of motor function, age, cognitive status, and psychiatric diagnosis. After controlling for spontaneous parkinsonism, 32% of patients met strict criteria for NIP after receiving an average of 43 mg/day chlorpromazine equivalents of a typical neuroleptic. Factors contributing to the development of NIP included older age, instrumentally derived tremor, baseline extrapyramidal signs, type of neuroleptic, and severity of dementia. The use of risperidone in a small subsample was not associated with NIP. These findings indicate that even after controlling for spontaneous extrapyramidal signs at baseline and their natural fluctuations, there is a substantial risk of NIP in older patients who are treated with very low doses of typical neuroleptics.

Brief evaluation of medication influences and beliefs: development and testing of a brief scale for medication adherence.

Purpose: The purpose of this study was to develop and test a brief scale (Brief Evaluation of Medication Influences and Beliefs [BEMIB]) designed to identify patients who are more likely to be nonadherent to their antipsychotic medication. Methods: Sixty-three outpatients with schizophrenia and related psychotic disorders were enrolled and given an assessment battery including the BEMIB, a previously published adherence scale, extrapyramidal symptom rating scales, and an adherence assessment with patient self-report and prescription refill records. The BEMIB consisted of 8 statements derived from the health belief model with a 5-point Likert-type scale for each statement. Subjects chose a single answer for each item depending on their level of agreement or disagreement. Results: According to refill records, subjects meeting BEMIB-based criteria for nonadherence had significantly larger gaps in antipsychotic therapy (greater nonadherence) compared with those of participants not meeting criteria for nonadherence. For the 1-week test-retest reliability, the BEMIB total score and 5 of 8 single items correlated significantly. BEMIB total scores correlated significantly with an established assessment of adherence (Drug Attitude Inventory), demonstrating adequate construct validity. Conclusion: The BEMIB represents a promising scale for identifying patients more likely to be nonadherent to their medications.

Adherence and persistence to typical and atypical antipsychotics in the naturalistic treatment of patients with schizophrenia

Objective To compare adherence and persistence to typical versus atypical antipsychotics and between specific atypical agents in the usual care of schizophrenia and to examine the association between adherence and persistence. Method Data were drawn from a 3-year prospective, nonrandomized, noninterventional study of schizophrenia conducted during 1997–2003. Initiators on haloperidol, risperidone, olanzapine, quetiapine, and clozapine with at least 1 year of follow-up were included (n = 878). Adherence (Medication Possession Ratio, MPR) and persistence (time to all-cause medication discontinuation) were assessed using medical record prescription information. Analyses employed multivariate statistics adjusted for group differences. Results Overall, 58% of the patients were deemed adherent (MPR >80%). Adherence rates were higher: for atypical (59.4%) than typical antipsychotics (34.5%, p < 0.001), for clozapine (77%) than each comparator excluding olanzapine (p < 0.01), and for olanzapine (64%) than risperidone (57%, p = 0.027) and quetiapine (52%, p = 0.019). Differences between risperidone and quetiapine were not statistically significant. Adherence and persistence were highly correlated (r = 0.957, p < 0.001). Conclusion In the usual care of schizophrenia, medication adherence and persistence appear to be highly correlated and to significantly differ between typical and atypical antipsychotics and among atypical agents. The choice of antipsychotic may play a meaningful role in patients’ adherence to and persistence with antipsychotic medications.

Newer antipsychotics and antidepressants for elderly people

The newer antipsychotics and antidepressants offer distinct clinical advantages over older agents.Specifically, treatment with the atypical antipsychotic agents clozapine and risperidone has resulted in greater reduction in negative symptoms associated with schizophrenia. Also, the atypical antipsychotic drugs have been associated with a lower risk of extrapyramidal symptoms, such as parkinsonism and tardive dyskinesia, relative to typical agents. For antidepressants, the safety profile of the selective serotonin reuptake inhibitors nefazodone and venlafaxine, in terms of anticholinergic side effects, cardiac toxicity, and overdose lethality, is superior to the older tricyclic antidepressants and monoamine oxidase inhibitors.

Do people with schizophrenia have differential impairment in episodic memory and/or working memory relative to other cognitive abilities?

Efforts to identify differential or core cognitive deficits in schizophrenia have been made for several decades, with limited success. Part of the difficulty in establishing a cognitive profile in schizophrenia is the considerable inter-patient heterogeneity in the level of cognitive impairment. Thus, it may be useful to examine the presence of relative cognitive weaknesses on an intra-person level. In the present study we examined the rates of significant intra-person differences between crystallized verbal ability versus five other cognitive abilities among 127 persons with schizophrenia or schizoaffective disorder and 127 demographically matched normal comparison (NC) subjects. We found that the rates of significant discrepancies above the NC group base-rates was significantly greater in reference to those discrepancies involving visual memory relative to those associated with auditory memory, working memory, processing speed, and perceptual organization. The findings conflict with prior suggestions that working memory or auditory episodic memory are differential or core deficits in schizophrenia, and highlight the importance of considering visual memory in characterizing the cognitive effects of this condition.