An open trial of adjunctive sertraline in the treatment of chronic schizophrenia

While the positive symptoms of schizophrenia are amenable to treatment with standard neuroleptics, negative symptoms are often difficult to treat. Co-prescribing antidepressants, such as sertraline, for patients on stable neuroleptic depot preparations is one pharmacological method of overcoming this problem. A total of 20 patients with chronic schizophrenia were enrolled in an open trial over a 12-week period during which sertraline was added to their usual antipsychotic medication. Prior to this, baseline scores for positive and negative symptoms, and extrapyramidal side-effects, were measured. The addition of sertraline resulted in global improvement, with a significant reduction in positive and negative symptom scores and no increase in undesirable neuroleptic side-effects. Sertraline may act by indirectly reducing dopaminergic activity.     

Clinical predictors of relapse following neuroleptic withdrawal.

The validity of previously hypothesized predictors of elapse following neuroleptic discontinuation was examined. One hundred sixty-two outpatients, with either Research Diagnostic Criteria schizophrenia or schizoaffective disorder, were discontinued from neuroleptic medication for a 28-day period or until judged to be relapsed. Pre-discontinuation neuroleptic dosage level, the severity of psychotic symptoms, and the presence of dyskinetic movements prior to neuroleptic discontinuation were the predictor variables. Of the 162 patients, 62.7% did not relapse during the study period. There were no differences in the survival rates between the patients withdrawn from oral versus depot neuroleptics. Neuroleptic dosage, but not severity of psychotic symptoms or dyskinetic movements, predicted relapse. These results support the hypothesis that pre-withdrawal neuroleptic dosage level predicts relapse, but fail to validate either severity of psychotic symptoms or presence of dyskinetic movements as predictors of relapse.     

Depot neuroleptic therapy: an underutilized treatment option.

BACKGROUND: Depot neuroleptics are effective as long-term maintenance therapy in chronic schizophrenia and are widely used in Europe. In the United States, however, physicians have been reluctant to use them. They assume that depot neuroleptics present an increased risk of major side effects, that patients do not accept or tolerate them as well as oral agents, and that prescribing depot neuroleptics increases the possibility of medicolegal problems. METHOD: We analyzed the published data on neuroleptic malignant syndrome, tardive dyskinesia, extrapyramidal symptoms, perceptions of depot therapy, and medicolegal concerns. Whenever possible, we used the Mantel-Haenszel test to compare the outcome of oral versus depot neuroleptic medication treatment. RESULTS: Depot neuroleptics are not associated with an increase in any of the negative outcomes assessed. CONCLUSION: Depot neuroleptics represent a valuable treatment option for many patients and merit wider use.     

Prevalence of and risk factors for medication nonadherence in patients with schizophrenia: a comprehensive review of recent literature

OBJECTIVE: Nonadherence to prescribed antipsychotic medications places patients with schizophrenia at a greatly increased risk of illness exacerbation and rehospitalization. Identification of risk factors for nonadherence is an initial step toward designing effective interventions. This article reviews recent literature on the prevalence of and risk factors for medication nonadherence in patients with schizophrenia. DATA SOURCES: We searched the MEDLINE/HealthSTAR and PsycINFO databases using combinations of the keywords risk factor(s), adherence, compliance, antipsychotic, neuroleptic, schizophrenia, and psychosis for articles published since 1980 that identified risk factors for medication nonadherence in schizophrenia patients. We included reports that (1) were published in English and (2) specifically examined risk factors for medication nonadherence. Thirty-nine articles met our selection criteria. DATA SYNTHESIS: Among the 10 reports that met a strict set of study inclusion criteria, we found a mean rate of nonadherence of 41.2%; the 5 reports that met a stricter set of inclusion criteria had a mean nonadherence rate of 49.5%. In the 39 articles reviewed, factors most consistently associated with nonadherence included poor insight, negative attitude or subjective response toward medication, previous nonadherence, substance abuse, shorter illness duration, inadequate discharge planning or aftercare environment, and poorer therapeutic alliance. Findings regarding an association between adherence and medication type were inconclusive, although few studies explored this relationship. Other factors such as age, gender, ethnicity, marital status, education level, neurocognitive impairment, severity of psychotic symptoms, severity of medication side effects, higher antipsychotic dose, presence of mood symptoms, route of medication administration, and family involvement were not found to be consistent predictors of nonadherence. Limitations of the published literature are discussed. CONCLUSION: Efforts to improve medication adherence in patients with schizophrenia should target relevant risk factors.     

Understanding adherence to neuroleptic treatment in schizophreniaí

Understanding the factors that impede and promote adherence by people with schizophrenia to neuroleptic medication is important for treatment planning and relapse prevention. A total of 184 DSM-IV schizophrenia inpatients were examined with the Rating of Medication Influences (ROMI) scale within a context of inpatient vocational rehabilitation. Confirmatory factor analysis was used to evaluate the underlying dimensions of compliance behavior. The three-dimensional model of Weiden and his associates was confirmed by this study; specific factors included influence of others, medication affinity, and prevention. Additional analyses examined cognitive variables, symptoms, and course variables as predictors of individual factors. Verbal memory and cognitive flexibility were found to be associated with influence of others. Possible consequences for designing compliance enhancing therapeutic interventions are discussed.     

Dysphoric subjective response to neuroleptics in schizophrenia: relationship to extrapyramidal side effects and symptomatology.

OBJECTIVE: Subjective reports of dysphoric responses to neuroleptic medication are common in clinical practice. However, cognitive and affective side effects of neuroleptic medications are difficult to differentiate from the symptoms of schizophrenia. We sought to elucidate the relative contribution of extrapyramidal side effects and symptomatology to dysphoric response. METHOD: Fifty clinically stable outpatients with schizophrenia attending a rehabilitation centre were assessed for extrapyramidal side effects and symptomatology before completing the drug attitude inventory (DAI). RESULTS: Presence of extrapyramidal side effects, found in 28 patients (Z = -1.99, p = 0.05), and severity of negative symptoms (r = -0.47, p = 0.001) were independently associated with dysphoric response, explaining a significant proportion of the variance (R = 0. 53, R(2) = 25.2%, F = 9.27, df = 2, p = 0.0004). CONCLUSIONS: Patients who report a dysphoric response which they associate with neuroleptic medications have more extrapyramidal side effects and more severe negative symptoms. While these responses may be part of the negative symptoms of the illness or due to other factors such as depression, we raise the possibility that they may be clinically indistinguishable from, and be a subjective measure of, the so-called 'neuroleptic-induced deficit syndrome'.     

Randomised clinical trial comparing oral versus depot formulations of zuclopenthixol in patients with schizophrenia and previous violence.

PURPOSE: The aim of this longitudinal study was to determine whether the depot formulation of an antipsychotic reduces violence in outpatients with schizophrenia as compared to oral administration of the same antipsychotic. METHODS: Forty-six previously violent patients with schizophrenia were randomised to receive treatment with oral or depot zuclopenthixol for 1 year. Clinicians interviewed patients at baseline and every month thereafter to assess treatment adherence. An interviewer blinded to treatment assignments interviewed an informant about any violent behaviour during the previous month. RESULTS: Violence during the follow-up year was inversely proportional to treatment adherence, better compliance, and greater reduction of positive symptoms. Lower frequency of violent acts was observed in the depot group. The level of insight at baseline was not significantly associated with violence recidivism. Regardless of route of administration, treatment non-adherence was the best predictor of violence. CONCLUSIONS: Some patients with schizophrenia and prior violent behaviour may benefit from the depot formulation of antipsychotic medication.     

Changes in plasma homovanillic acid concentrations in schizophrenic patients following neuroleptic discontinuation.

Changes in plasma levels of the dopamine metabolite homovanillic acid have been reported to correlate with changes in the severity of schizophrenic symptoms during neuroleptic administration and after neuroleptic discontinuation. This study examined the effects of discontinuation of neuroleptic treatment on plasma homovanillic acid levels in 23 patients with chronic schizophrenia. It was hypothesized that clinical decompensation would be associated with increased plasma homovanillic acid levels. Plasma homovanillic acid was measured during administration of neuroleptic medication and during a subsequent 6-week drug-free period. Nine patients decompensated during the drug-free period and 14 patients did not. Following drug discontinuation, plasma homovanillic acid concentrations were higher in schizophrenic patients who decompensated than in those who did not. Furthermore, peak plasma homovanillic acid elevation after discontinuation of neuroleptic medication was significantly correlated with peak Brief Psychiatric Rating Scale increase. The data suggest that, in some schizophrenic patients, symptomatic decompensation after discontinuation of neuroleptic treatment is associated with increases in dopamine turnover.     

Which factors affect treatment response in late paraphrenia?

Sixty-four patients with late paraphrenia who had been prescribed neuroleptic treatment for at least three months in the previous year were clinically reviewed in order to asses their treatment response. At the time of assessment, 42.2% of the patients showed no response, 31.3% a partial response and 26.6% a full response to treatment. Compliance with medication, receiving depot rather than oral medication, and use of a community psychiatric nurse if the patient was an outpatient all had a positive effect on treatment response. Despite their better treatment response rate, patients prescribed depot medication received on average a lower daily dose in chlorpromazine equivalents than those prescribed oral medication. Improved compliance, greater clinical efficacy and a reduction in the dose of neuroleptic medication administered are all good reasons to commence treatment of late paraphrenia with a depot antipsychotic medication.     

Plasma phenylethylamine in schizophrenic patients

Plasma samples were collected from 41 patients who met DSM-III criteria for schizophrenia and from 34 healthy controls. Phenylethylamine (PE) levels were determined using a gas chromatography-mass spectrometry negative chemical ionization method. PE was significantly higher in the schizophrenic patients compared with controls. There were no differences in PE between paranoid and nonparanoid patients. Plasma PE did not appear to be influenced by the severity of schizophrenic symptoms (rated by BPRS, SANS, and SAPS) or by the amount of dietary phenylalanine ingested within 24 hr of testing. Plasma PE did not correlate with current or past exposure to neuroleptic medication. It was not possible, however, to test individual patients during two periods when they were taking and not taking medication. Thus it is possible that neuroleptic exposure may have confounded the results. This study provides further evidence that PE excess may play a role in the etiology of schizophrenia but does not support previous studies which suggest that such an abnormality is limited to the paranoid subgroup.     

Adherence assessments and the use of depot antipsychotics in patients with schizophrenia

BACKGROUND: Antipsychotic medications significantly ameliorate the symptoms of schizophrenia, but patients are often noncompliant with these medications. Research evidence supports the use of depot antipsychotics in noncompliant patients. METHOD: Between January 9, 1991, and December 19, 1995, 1307 veterans with schizophrenia or schizoaffective disorder (ICD-9) were enrolled in a study of enhanced psychosocial programming at 14 Veterans Administration Medical Centers. All had a history of high inpatient use. At enrollment, clinicians listed patient medications, rated patient compliance, and completed a Brief Psychiatric Rating Scale (BPRS) and Global Assessment of Functioning (GAF). Patients reported medication side effects. We describe depot antipsychotic use among these patients and examine the relationship between depot use, assessed compliance, and patient characteristics. RESULTS: At enrollment, 18% of patients in this cohort were receiving depot antipsychotics; however, clinicians reported that 49% had been noncompliant with medication in the past year. Depot use varied significantly with treatment site; African Americans were more likely to receive depot antipsychotics and less likely to receive atypical antipsychotics than white patients. Patients on depot and oral agents had similar levels of psychiatric symptoms, but patients on depot antipsychotics were more likely to receive high doses and complain of side effects. CONCLUSION: Clinicians prescribed depot antipsychotics relatively infrequently, despite high rates of noncompliance and high levels of inpatient use. Variation in use with treatment site and ethnic group suggests barriers to implementing research-based recommendations for depot use in noncompliant patients. Quality improvement programs should consider facilitating the appropriate use of depots.     

Predictors of compliance with neuroleptic medication among inpatients with schizophrenia: a discriminant function analysis.

OBJECTIVE: To identify clinically useful predictors of adherence to medication among persons with schizophrenia. METHOD: We evaluated levels of compliance with neuroleptic medication among 32 consecutive admissions with DSM-III-R schizophrenia from a geographically defined catchment area using a compliance interview. We also assessed symptomatology, insight, neurological status and memory. RESULTS: Less than 25% of consecutive admissions reported being fully compliant. Drug attitudes were the best predictor of regular compliance, symptomatology the best predictor of noncompliance, and memory the best predictor of partial compliance with neuroleptic medication. CONCLUSIONS: These data emphasise the complexity of factors that influence whether a person adheres to his medication regimen. Furthermore, they suggest that these factors may vary within the same person over time.     

Three years' maintenance neuroleptic treatment in schizophrenia--before and beyond.

A group of patients with schizophrenia, initially 67 patients, was studied over a period of 3 years. After three years 36 out of 67 patients were still on the same depot neuroleptic. The main aim was to describe and compare maintenance neuroleptic therapy using two depot neuroleptics, fluphenazine decanoate and pipotiazine palmitate, given monthly. Before the outpatient care the patients had participated in the department's comprehensive hospital treatment including depot neuroleptic medication. After a 1-year clinical trial with frequent assessments of the patients, significant symptom reductions were found on all rating scales. During the last 2 years of the study only drug therapy was given. Improvement concerning social function in the community and work level as well as the low-rated psychopathology noted at the start of study also persisted at the 3-year follow-up. The side effects were low in frequency and quality. These results show the clinical value of long-term maintenance treatment with depot neuroleptics. The results also confirm that the favourable effects of the hospital treatment demonstrated before the start of the clinical trial could be maintained. The possibilities of further improving aftercare and outpatient treatment beyond medication alone are discussed.     

Reducing the dose of depot neuroleptics in stable schizophrenia.

In order to determine the safety of reducing maintenance neuroleptic dose in long-term ambulatory schizophrenia, a step-wise depot reduction study was carried out on patients over a six month period. Doses were reduced by 1/8 of original approximately every two months for a total of three reductions. At the end of dose reduction and at six month follow-up, relapse rate was calculated. Relapse in this study was defined as the clinical decision to either increase neuroleptic dose or to hospitalize. Approximately 50% of the patients relapsed. There was no association with life events as measured by the Paykel scale. Where relapse occurred, it was usually seen subsequent to the second dose reduction. Patients who survived dose reduction had been maintained for a significantly longer period on depot neuroleptics and tended to suffer from a form of schizophrenia which required the co-administration of antidepressants. The findings show that, for a population on long-term depot medication, the risk of symptom exacerbation after gradual step-wise neuroleptic reduction is 50%. The results help to delineate which patients will fall into that 50%.     

Neuroleptic treatment of late-life schizophrenia

There is a paucity of studies on the use of neuroleptic medication for treatment of the core symptoms of schizophrenia in elderly patients. The studies that are available have significant methodologic problems, including the mixing of early- and late-onset patients, inadequate outcome criteria, and the lack of control groups. Studies of conventional neuroleptics suggest that older patients have a moderate therapeutic response but are likely to develop side effects. The few studies of atypical antipsychotics now available suggest efficacy for treatment of behavioral disturbance in the elderly and a more favorable side-effect profile. The usefulness of all neuroleptics for the treatment of the core symptoms of late-life schizophrenia may depend on the duration and severity of the symptoms, with a poor response associated with greater severity and duration. It appears that patients with later-onset symptoms may respond better to all neuroleptics.     

Comparative efficacy of long-acting depot and oral neuroleptic medications in preventing schizophrenic recidivism

Two health service data bases provided data on the use of neuroleptic medications in the maintenance therapy of schizophrenic patients in the Canadian province of Saskatchewan. The pattern of prescribing medication appeared to be influenced by the bed-to-population ratio. For 1235 discharged schizophrenic patients, the 2-year rehospitalization rate (56%) was higher than expected. Although oral maintenance therapy predominated, patients maintained on long-acting depot neuroleptic medication had a significantly lower (p less than .05) rehospitalization rate than those on oral preparations. The highest rehospitalization rate was found among patients prescribed combined depot and oral preparations, confirming the ineffectiveness of combined medication. Using data bases avoided the sampling bias inherent in prospective controlled trials and provided a complementary epidemiologic dimension to the study of maintenance neuroleptic therapy of schizophrenia under normal treatment conditions.     

The use of Depot neuroleptics in the elderly: A survey

A survey of psychiatric services across a city revealed 98 elderly patients who were receiving depot neuroleptics. Most had a diagnosis of schizophrenia, affective illness or paraphrenia and the majority received ‘depot’ as their only psychotropic medication. Extrapyramidal side-effects as judged by psychiatric nurse key workers were significantly associated with high total neuroleptic dose (100 mg ‘chlorpromazine equivalent’ or more). Those with a diagnosis of paraphrenia were maintained on a lower median dose of ‘depot’ than their schizophrenic of affectively ill counterparts. Large differences in practice, not readily explained by case mix, but perhaps understandable in view of large variations in nursing workload, were observed.     

A 15-year open study on a cohort of West-African out-patients with a chronic psychosis

BACKGROUND: We wanted to find out if the additional costs of depot neuroleptic in comparison to oral medication was justified by a decrease in admission days. METHODS: An open study on a cohort of chronic psychotic out-patients (n=45) consisting of a retrospective 10-year period on oral medication followed by a prospective 5-year period of treatment with haloperidol decanoate. After recording socio-demographic characteristics and a DSM-III-R diagnosis, patients were assessed before and after the administration of depot neuroleptic with the BPRS, the NOSIE, the SDRS and a list of side effects. A semi-structured interview was conducted with the patients and their families to ask about the change in social relationships with family members and other people after starting the depot treatment. Social intervention was limited to involvement of the family in the monthly depot medication outpatient clinic and to an explanation of the rationale of follow-up treatment and deinstitutionalisation of psychiatric care in the village of origin. RESULTS: The number of admission days decreased from an average of 100 days a year on oral medication to 5 days a year on depot neuroleptic. Patients report a sharp decrease in symptoms paralleled by an increase in social functioning over the first 3 months. After 6-9 months this pattern stabilised and was maintained over the period from 1 to 5 years whereas the dosage was further decreased to an average of 1 cc decanoate or 20 haldol equivalents monthly. CONCLUSIONS: This study suggests that depot neuroleptic in the context of a public mental health approach is a highly effective and feasible treatment for West African patients suffering from a chronic functional psychosis.     

Schizophrenic patients' subjective reasons for compliance and noncompliance with neuroleptic treatment

Although several factors influencing schizophrenic patients' compliance with neuroleptic treatment have been investigated, the subjective reasons that patients are willing or reluctant to take medication have rarely been examined. In a follow-up study of a sample of schizophrenic patients currently undergoing psychiatric treatment in the city of Leipzig, 307 patients were asked about their subjective reasons for medication compliance or noncompliance by administering the Rating of Medication Influences (ROMI) Scale. The perceived benefit from medication proved to be the main reason for patients' compliance with neuroleptic treatment. Respectively, patient-reported noncompliance was mainly explained by negative side effects of medication. However, there were no statistically significant differences in responses between the patients receiving conventional versus second-generation antipsychotics. A positive relationship with the therapist and a positive attitude of significant others toward neuroleptic treatment contributed to patients' medication compliance. Reasons for noncompliance with neuroleptic treatment were lack of acceptance of the necessity of pharmacological treatment and lack of insight into the disease. The results emphasize the importance of psychoeducation in enhancing patient compliance with neuroleptic treatment.