Clozapine augmentation with cariprazine for negative symptoms: a case series and literature review.

Only about 50% of patients with treatment-resistant schizophrenia respond to clozapine, and many more patients continue to experience ongoing and prominent negative symptoms. These negative symptoms, for which there are limited pharmacological options, may represent the greatest barrier to functional recovery. Cariprazine is a novel antipsychotic drug that is a partial agonist at dopamine D2 and D3 receptors with preferential binding to the D3 receptor, antagonism of 5HT2B receptors, and partial agonism at 5HT1A receptors. Cariprazine is currently licenced for the treatment of schizophrenia in Europe and the United States and has also been approved for bipolar disorder in the United States. There is a limited body of evidence to suggest clinical effectiveness as an augmentation strategy for negative symptoms in those treated with clozapine. In this case series, we present five cases of successful treatment of negative symptoms by clozapine combined with cariprazine in treatment-resistant psychosis.

Incident infection during the first year of treatment - A comparison of clozapine and paliperidone palmitate long-acting injection.

BACKGROUND: To examine the risk of infection in patients prescribed clozapine compared with patients prescribed paliperidone palmitate long-acting injection (PPLAI). METHOD: A retrospective, 1-year, cohort study conducted on events occurring in eligible patients beginning treatment for the first time with clozapine or PPLAI between June 2017 and June 2019 in a UK mental health trust providing in-patient and out-patient services. RESULTS: The study included 64 patients starting clozapine and 120 patients starting PPLAI. Incidence of infection was greater in clozapine starters than in PPLAI starters (28% vs 6%; p = 0.001; adjusted odds ratio 5.82 (95% confidence interval (CI) = 2.15-15.76, p = 0.001). Infectious episodes in clozapine patients were not related to changes in neutrophil counts. Incident infection in the clozapine group was highest in the first 3 months of treatment. The most commonly reported infection in the clozapine group was chest infection; however, the majority of infections were non-chest-related. CONCLUSION: Patients starting clozapine showed a substantially increased likelihood of infection compared with patients starting PPLAI.

Positive views on antipsychotic long-acting injections: results of a survey of community patients prescribed antipsychotics.

BACKGROUND: We aimed to assess patients' views about antipsychotic long-acting injections (LAIs). METHODS: We interviewed patients prescribed an antipsychotic (oral or LAI) in our community teams. In a subanalysis, responses were analysed for differences between patients currently receiving an LAI and those prescribed only oral medication. RESULTS: In total, 226 patients (57%) completed the study questionnaire. The majority agreed that LAIs ensured delivery of the right amount of medication and protection against hospital admissions (57% and 60%, respectively). A minority of participants were more concerned than not about the use of a needle (46%), pain from injection (48%) and the need to travel to receive the injection (34%). A majority expressed a preference for injection site (deltoid or gluteal) (65%) and clinic location (69%). A higher proportion of patients currently receiving an LAI compared with those prescribed oral medication thought an LAI was beneficial because this formulation obviated the need to: swallow tablets (63% versus 41%; p = 0.0013), remember to take tablets daily (75% versus 51%; p = 0.0004), remember tablets when away from home (72% versus 49%; p = 0008). Current LAI users were more likely than those on oral treatment to agree that LAIs keep patients out of hospital (76% versus 44%; p = 0.0001) and that the injection ensured delivery of the right amount of medication (71% versus 44%; p = 0.0002). Women were more likely than men to prefer administration by a clinician of the same gender (34% versus 12%; p = 0.0001). CONCLUSIONS: In our study, a greater proportion of patients prescribed an LAI regarded LAIs as beneficial compared with those on oral medication.

Haloperidol decanoate long-acting injection (HDLAI): Results of a 1-year mirror-image study.

BACKGROUND: We sought to determine clinical outcomes of the prescribing of haloperidol decanoate long-acting injection (HDLAI) at 1 year. METHOD: A 1-year mirror-image study of 84 inpatients initiated on HDLAI. Admissions and bed days in the year preceding HDLAI were compared with the year after initiation. Predictors for discontinuation were evaluated. RESULTS: At 1 year, 33% of patients remained on treatment. Patients starting HDLAI because of nonadherence were more likely to stop treatment [relative risk (RR) 1.72; 95% confidence interval (CI) 1.01, 2.91; p = 0.044] whilst patients with a longer duration of illness were more likely to remain on treatment (RR 0.88; 95% CI 0.78, 1.00; p = 0.050). In the bed days cohort overall, (n = 65), there was a significant reduction in mean hospital admissions (1.4/patient/year to 0.6/patient/year; p = 0.0001) but not bed days (55.6/patient to 45.0/patient; p = 0.07) in the year following HDLAI initiation compared with the year before. Continuers had a significant reduction in mean bed days (53.1 to 4.0; p = 0.0002) and hospital admissions (1.5 to 0.2; p = 0.0001). Discontinuers demonstrated a significant reduction in hospital admissions (1.5 to 0.8; p = 0.0001) but not bed days (56.7 to 64.5; p = 0.83). CONCLUSION: HDLAI was associated with a high treatment discontinuation rate. Hospital admissions fell in the year after HDLAI but there was no change in bed days. Our study suggests that patients with a longer duration of illness and patients initiated on HDLAI for reasons other than poor adherence may benefit from HDLAI initiation.

A prospective year-long follow-up of lurasidone use in clinical practice: factors predicting treatment persistence.

BACKGROUND: Our aim was to follow up patients prescribed lurasidone over 1 year to determine factors predicting treatment persistence. METHODS: We used noninterventional, observational, prospective follow up of patients consecutively prescribed lurasidone in a large inner-city NHS mental health trust. We also performed retrospective analysis of outcomes from patient case notes. RESULTS: Data were available for 69 patients consecutively prescribed lurasidone, of whom three (4%) were lost to follow up. Out of the 66 patients not lost to follow-up, 21 (32%) remained on lurasidone at 1 year. The main reasons for discontinuation were perceived ineffectiveness (49% of discontinuers) and adverse effects (36% of discontinuers), whilst a further seven refused all treatment. Median treatment time on lurasidone was 154 days (95% confidence interval (CI), 33-275). Patients who were not treatment-resistant had a substantially reduced risk of discontinuation, relative risk (RR) 0.18 [95% CI 0.08, 0.41, p < 0.001]. Medium doses (>37-74 mg) of lurasidone reduced the risk of discontinuation by 75% [RR 0.25 (95% CI 0.11, 0.58, p = 0.001)]; high doses (>74-148 mg) reduced the risk of discontinuation by 86% [RR 0.14 (95% CI 0.06, 0.35, p < 0.001)]. Risk of discontinuation was approximately doubled when the reason for prescribing lurasidone was poor tolerability of prior treatment [RR 2.01 (95% CI 1.05, 3.85, p = 0.035)]. CONCLUSION: The likelihood of treatment continuation with lurasidone can be vastly improved by targeting individuals most likely to benefit and by using optimal doses.

Reducing the rates of prescribing high-dose antipsychotics and polypharmacy on psychiatric inpatient and intensive care units: results of a 6-year quality improvement programme.

BACKGROUND: There is no conclusive evidence that either high doses or combinations of antipsychotics are more effective than standard doses or monotherapy alone. Nonetheless, prescription of both remains prevalent in the UK. In 2006 the South London and Maudsley NHS Foundation Trust (SLAM) participated in a national survey of prescription of antipsychotic medications, organized by the Prescribing Observatory for Mental Health. Over half of the patients on SLAM inpatient or psychiatric intensive care units were prescribed a high-dose antipsychotic or a combination of antipsychotics. Prescribing high-dose antipsychotics and polypharmacy in SLAM was found to be among the highest in the UK. AIM: To assess the impact of a 6-year quality improvement programme aimed at reducing the rates of prescribing high-dose antipsychotics and polypharmacy on SLAM inpatients and psychiatric intensive care units. RESULTS: There was a significant reduction between baseline and final survey in the rates of prescription of both high-dose antipsychotics and polypharmacy on SLAM inpatients and intensive care units (58% versus 10% p < 0.0001 and 57% versus 16%, p < 0.0001 respectively). The proportion of patients at final survey prescribed a high-dose antipsychotic and a combination was substantially lower in SLAM than in the national sample (10% versus 28%, p < 0.0001 and 16% versus 38%, p < 0.0001 respectively). CLINICAL IMPLICATIONS: A sustained change in the prescribing culture of an organization can be achieved through a targeted improvement programme.

Aripiprazole: dose-response relationship in schizophrenia and schizoaffective disorder.

Aripiprazole is an atypical antipsychotic that has been shown to be more effective than placebo and at least as effective as haloperidol and risperidone in the treatment of schizophrenia and schizoaffective disorder. Despite having a well defined licensed dose range, the optimum dose for aripiprazole is yet to be established. Aripiprazole exhibits high affinity for dopamine D(2) receptors, with near maximal receptor occupancy at a dose of 30 mg. Even doses as low as 2 mg, thought not to be clinically effective, have produced striatal D(2) receptor occupancies exceeding 70%, higher than the accepted threshold for antipsychotic effect. In this review we examined the efficacy data from short-term studies of aripiprazole in relapsed schizophrenia or schizoaffective disorder, in order to establish a dose-response relationship for aripiprazole. Results of five fixed-dose studies suggest that the threshold for clinical effect is between 5 and 10 mg/day. In addition, the highest response rate is seen at 10 mg/day. Doses above 20 mg/day do not appear to provide any additional benefit and may be associated with a smaller change in symptom scores. In summary, the data available so far indicate that the optimum dose for aripiprazole is 10 mg/day and that doses above 20 mg/day provide no additional benefit.

A prescription survey of antipsychotic use in England and Wales following the introduction of NICE guidance.

Objective : In the United Kingdom (UK) the National Institute for Clinical Excellence (NICE) has recommended the use of atypical antipsychotics for the treatment of schizophrenia. As part of its guidance it discourages the concurrent use of typical and atypical antipsychotics. In previous prescribing surveys antipsychotic polypharmacy has been noted to be widespread. We sought to evaluate atypical antipsychotic prescribing after the publication of NICE guidance. Method : We invited psychiatric centres in England and Wales to participate, in March 2004, in an atypical antipsychotic prescribing survey of hospital in-patients. Results : Thirty-six in-patient units submitted data for 2012 patients. After exclusions, 1092 patients were eligible. Of these, 28.6% (312) were prescribed a typical alongside an atypical antipsychotic and 19.3% (211) were prescribed high-dose antipsychotics. Co-prescription was more prevalent in patients aged 40 years and above (32.0 vs. 25.3%; P=0.018). It was also noted that in centres employing senior pharmacists, co-prescription was more common (28.6 vs. 14.3%; P=0.03). High-dose treatment was more commonly observed in patients of a white ethnic background (20.6 vs. 13.9%; P=0.02) as well as in patients aged 40 years and above (24.4 vs. 15.0%; P<0.001). Prescription of anticholinergics was significantly more prevalent in those receiving atypical and typical combinations than atypicals alone (26.0 vs. 12.0%; P<0.001). Conclusions : Antipsychotic polypharmacy remains commonplace. Similarly the prescription of high-dose antipsychotics is also widespread.

Early clinical experience with risperidone long-acting injection: a prospective, 6-month follow-up of 100 patients.

BACKGROUND: The use of risperidone long-acting injection (RLAI) is reasonably well supported by controlled studies. Little is known about treatment outcomes in patients receiving RLAI in clinical practice. METHOD: All prescribers in the South London and Maudsley Trust, London, United Kingdom, were informed that RLAI could be ordered for suitable patients with a DSM-IV diagnosis of schizophrenia or schizo-affective disorder: those known to be noncompliant with oral atypical antipsychotics and those intolerant of the adverse effects of conventional depot antipsychotics. Prescribers provided treatment and clinical progress data at the time of each prescription. Data collected included reason for prescribing RLAI, Clinical Global Impressions scale (CGI) score, inpatient or out-patient status, and details of all medications prescribed. All treatment discontinuations were investigated. The study was conducted from August 2002 to August 2003. RESULTS: Outcome could be determined for 100 subjects. Seventy-nine subjects (79%) were hospitalized when RLAI was initially prescribed. Mean duration of stay before RLAI initiation was 97 days (range, 0-1492 days). Most subjects were switched to RLAI from oral atypical (58%) or conventional depot (28%) antipsychotics. The main reason given for prescribing RLAI was poor patient acceptability of previous treatments (79%). Overall, 51% of the subjects discontinued RLAI. The main reason for discontinuation was lack of effect (24 subjects). No patient-related factor predicted outcome. CGI scores improved from a mean of 4.7 to 3.6 over the study period (p <.001). Overall, 61 subjects (61%) showed an improvement in CGI scores between baseline and endpoint. Antipsychotic coprescriptions were reduced from 71% of subjects to 8%. In completers, 23 (61%) of 38 subjects beginning RLAI as inpatients were discharged. The modal dose of RLAI was 25 mg every 2 weeks. CONCLUSION: RLAI was moderately effective in clinical practice as judged by attrition from treatment. CGI score changes and discharge rates also suggest moderate effectiveness. RLAI was well tolerated. Antipsychotic coprescription was infrequent.