Expert: Ivan Goldberg, M.D. - 7/8/2008

Question
How long is this injection effective?  Where can I find out more info on this?  My
daughter  is 21 and diagnosed bipolar.  She refuses treatment.  Thankyou

Answer
Jamie . . .

Injectable long-acting antipsychotic medications are used to treat people with schizophrenia, bipolar disorder and other serious psychiatric conditions.

below you will find some abstracts of articles from medical journals which should give you a good deal of hopefully useful information.

Best regards . . .

Ivan
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1: J Nerv Ment Dis. 2007 Dec;195(12):976-82.Related Articles, Links
The impact of insight on functioning in patients with schizophrenia or schizoaffective disorder receiving risperidone long-acting injectable.

Gharabawi G, Bossie C, Turkoz I, Kujawa M, Mahmoud R, Simpson G.

Ortho-McNeil Janssen Scientific Affairs, L.L.C., Titusville, New Jersey, USA.

This post hoc analysis explored the role of insight as a mediator of functioning in a 52-week, double-blind, international trial of 323 patients with schizophrenia or schizoaffective disorder receiving risperidone long-acting injectable. Measures included the Positive and Negative Syndrome Scale (PANSS) insight item, PANSS factors, Clinical Global Impressions-Severity (CGI-S), Strauss-Carpenter Levels of Functioning (LOF), Personal and Social Performance (PSP) scale, and a cognitive test battery. Correlation/regression analyses examined associations between demographic and clinical characteristics, including insight, and functional measures. Insight scores correlated significantly with CGI-S, PANSS subscales, PSP, LOF, and several cognitive measures. Regression models demonstrated that changes in insight, changes in negative symptoms, and study duration were significantly associated with PSP and LOF total change scores. Findings identified important variables to consider for intervention to improve functioning in schizophrenia.

Publication Types:
Comparative Study
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

PMID: 18091190 [PubMed - indexed for MEDLINE]

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2: Schizophr Bull. 2007 Nov;33(6):1379-87. Epub 2007 Apr 29.Related Articles, Links
Treatment of schizophrenia with long-acting fluphenazine, haloperidol, or risperidone.

Olfson M, Marcus SC, Ascher-Svanum H.

Division of Clinical and Genetic Epidemiology, New York State Psychiatric Institute, New York, NY, USA. mo49@columbia.edu

OBJECTIVE: This study compares 3 cohorts of patients with schizophrenia before, during, and after initiating treatment with fluphenazine decanoate (FD), haloperidol decanoate (HD), or long-acting injectable risperidone (LAR). METHODS: Administrative data are analyzed from California Medicaid (Medi-Cal) beneficiaries with schizophrenia who initiated FD, HD, or LAR treatment. Patients were required to have been continuously enrolled in Medi-Cal for 180 days before and 180 days after the start of the new episode of long-acting antipsychotic therapy. RESULTS: There were few demographic and clinical differences among patients initiating FD, HD, and LAR. During the 180 days before starting long-acting injections, most patients initiating FD (53.5%), HD (58.5%), and LAR (61.2%) received oral antipsychotic medications for <80% of the days in this period (medication possession ratio: <0.80). The mean duration of depot treatment episodes was 58.3 days (SD = 53.6) for FD, 71.7 days (SD = 56.4) for HD, and 60.6 days (SD = 48.8) for LAR (F = 18.3, df = 2, 2694, P < .0001, HD > FD). Few patients who started on FD (5.4%), HD (9.7%), or LAR (2.6%) continued for at least 180 days. Most patients in each group (FD [77.4%], HD [78.9%], and LAR [75.5%]) received oral antipsychotic medications during the 45 days after discontinuing long-acting injections. Coprescription with antidepressants, mood stabilizers, and benzodiazepines was common. CONCLUSIONS: Patients treated with long-acting antipsychotic injections tend to have complex pharmacological regimens and recent medication nonadherence. A great majority of patients initiating long-acting antipsychotic medications discontinue use within the first few months of treatment.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 17470444 [PubMed - indexed for MEDLINE]

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3: J Psychopharmacol. 2005 Sep;19(5 Suppl):5-14.Related Articles, Links
Patients in the early phases of schizophrenia and schizoaffective disorders effectively treated with risperidone long-acting injectable.

Parellada E, Andrezina R, Milanova V, Glue P, Masiak M, Turner MS, Medori R, Gaebel W.

Clinic Schizophrenia Program, Department of Psychiatry, Clinical Institute of Neurosciences, Hospital Clinic de Barcelona, University of Barcelona, Barcelona, Spain. eparella@clinic.ub.es

The efficacy and safety of risperidone long-acting injectable (RLAI) was investigated in patients in the early phases of schizophrenia and schizoaffective disorders (< or = 3 years). Patients who required a treatment change received RLAI (2-weekly gluteal injections of 25, 37.5 or 50 mg, per clinical judgement), without an oral risperidone run-in phase.A total of 382 patients were included in this 6-month open-label study; 73% of patients completed the study. A total of 84% had schizophrenia with a median duration of 1.0 year since diagnosis. Previous medications were mainly atypical antipsychotics (70%) and depot neuroleptics (24%). The main reasons for treatment change were non-compliance (42%) and insufficient efficacy (31%) of previous medication. The total Positive and Negative Syndrome Scale (PANSS) and all its subscale scores improved significantly (p < or = 0.0001), with 40% of patients showing a 20% improvement on total PANSS. Global Assessment of Functioning, quality of life, patient satisfaction and movement disorders also improved significantly. Tolerability of RLAI was generally good and no unexpected adverse events were reported.The ensured delivery of medication with RLAI resulted in significant symptom improvement in this patient population. Direct initiation of RLAI is well accepted by patients. RLAI might represent a novel option for patients in the early phases of psychosis.

Publication Types:
Clinical Trial

PMID: 16144781 [PubMed - indexed for MEDLINE]

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4: Cochrane Database Syst Rev. 2005 Jul 20;(3):CD001717.Related Articles, Links
Update of:
Cochrane Database Syst Rev. 2000;(2):CD001717.

Depot perphenazine decanoate and enanthate for schizophrenia.

David A, Quraishi S, Rathbone J.

Institute of Psychiatry and GKT School of Medicine, King's College School of Medicine and Dentistry, 103 Denmark Hill, London, UK, SE5 8AF. a.david@iop.kcl.ac.uk

BACKGROUND: Antipsychotic drugs are usually given orally but compliance with medication given by this route may be difficult to quantify. The development of depot injections in the 1960s gave rise to extensive use of depots as a means of long-term maintenance treatment. Perphenazine decanoate and enanthate are depot antipsychotics that belong to the phenothiazine family and have a piperazine ethanol side chain. OBJECTIVES: To assess the effects of depot perphenazine decanoate and enanthate versus placebo, oral antipsychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes. SEARCH STRATEGY: We updated previous searches of the Cochrane Schizophrenia Group Register (June 1998), Biological Abstracts (1982-1998), the Cochrane Library (Issue 2, 1998), EMBASE (1980-1998), MEDLINE (1966-1998), and PsycLIT (1974-1998) by searching the Cochrane Schizophrenia Group Register (March 2004). References of all identified trials were also inspected for more studies and industry contacted. SELECTION CRITERIA: We compared randomised clinical trials focusing on people with schizophrenia where depot perphenazine decanoate and enanthate, oral antipsychotics or other depot preparations. DATA COLLECTION AND ANALYSIS: We reliably selected studies, quality rated them and extracted data. For dichotomous data we estimated the Relative Risk (RR) with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat statistic (NNT). Analysis was by intention-to-treat. MAIN RESULTS: Only four studies (Ahlfors 1980, Eufe 1979, Knudsen 1985c, Tegeler 1979), randomising a total 313 people could be included in this review and this combined with an overall lack of usable data limits any interpretation of results. Perphenazine enanthate was not significantly any better or worse than other depot antipsychotics in most of the main outcomes such as global state, relapse or leaving the study early. We found some differences favouring the control groups for adverse effects.One study (Ahlfors 1980) of six months' duration (n=172), compared perphenazine enanthate to clopenthixol decanoate. There were no differences between the two groups for outcomes of global improvement, relapse and leaving the study early. More people in the perphenazine enanthate group, however, required anticholinergic drugs than those allocated to clopenthixol decanoate (RR 1.12 CI 1.0 to 1.2, NNT 10).A single study (n=64, duration six weeks) compared perphenazine enanthate and its longer acting decanoate ester. Data on relapse and leaving the study early failed to show convincing differences. The enanthate group, however, experienced more movement disorders (RR 1.36, CI 1.1 to 1.8 NNT 5) than those allocated the decanoate ester of the same drug and required more anticholinergic drugs (RR 1.47 CI 1.1 to 2.0, NNT 4). AUTHORS' CONCLUSIONS: Depot perphenazine is in clinical use in the Nordic countries, Belgium, Portugal and the Netherlands. At a conservative estimate, a quarter of a million people suffer from schizophrenia in those countries and could be treated with depot perphenazine. The total number of participants in the four trials with useful data is 313. None of the studies observed the effects of oral versus depot antipsychotic drugs. Until well conducted and reported randomised trials are undertaken clinicians will be in doubt as to the effects of perphenazine depots and people with schizophrenia should exercise their own judgement or ask to be randomised.

Publication Types:
Review

PMID: 16034865 [PubMed - indexed for MEDLINE]

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5: J Clin Psychiatry. 2004 Aug;65(8):1076-83.Related Articles, Links
Early clinical experience with risperidone long-acting injection: a prospective, 6-month follow-up of 100 patients.

Taylor DM, Young CL, Mace S, Patel MX.

Pharmacy Department, Maudsley Hospital, London, United Kingdom. david.taylor@slam.nhs.uk

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.

Publication Types:
Clinical Trial
Comparative Study

PMID: 15323592 [PubMed - indexed for MEDLINE]

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6: Cochrane Database Syst Rev. 2004;(3):CD001719.Related Articles, Links
Update of:
Cochrane Database Syst Rev. 2000;(2):CD001719.

Depot bromperidol decanoate for schizophrenia.

Wong D, Adams CE, David A, Quraishi SN.

Academic Department of Psychiatry and Behavioural Sciences, University of Leeds, 15 Hyde Terrace, Leeds, West Yorkshire, UK, LS2 9LT. ugm0dwcw@leeds.ac.uk

BACKGROUND: Antipsychotic drugs are the mainstay treatment for schizophrenia. Long-acting depot injections of drugs such as bromperidol decanoate are extensively used as a means of long-term maintenance treatment. OBJECTIVES: To assess the effects of depot bromperidol versus placebo, oral antipsychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes. SEARCH STRATEGY: Relevant trials were identified by searching Biological Abstracts (1982-1999), Cochrane Library (Issue 2, 1999), Cochrane Schizophrenia Group's Register (May 1999), EMBASE (1980-1999), MEDLINE (1966-1999) and PsycLIT (1974-1999). References of all identified trials were inspected and Janssen-Cilag was contacted in order to identify more trials. An update search was undertaken in October 2003. The Schizophrenia Groups trials register is based on regular searches of BIOSIS Inside; CENTRAL; CINAHL; EMBASE; MEDLINE and PsycINFO; the hand searching of relevant journals and conference proceedings, and searches of several key grey literature sources. A full description is given in the Group's module. SELECTION CRITERIA: All randomised trials focusing on people with schizophrenia where depot bromperidol, oral antipsychotics or other depot preparations were sought. Primary outcomes were death, clinically significant change in global function, mental state, relapse, hospital admission, adverse effects and acceptability of treatment. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers and cross-checked. Fixed effects relative risks (RR) and 95% confidence intervals (CI) were calculated for dichotomous data. Weighted or standardised means were calculated for continuous data. Where possible, the number needed to treat statistic (NNT) was calculated. Analysis was by intention-to-treat. MAIN RESULTS: Four controlled clinical trials were included (total n=117). We identified a single small study of six months duration comparing bromperidol decanoate with placebo injection. Similar numbers left the study before completion (n=20, 1 RCT, RR 0.4 CI 0.1 to 1.6) and there was no clear differences between bromperidol decanoate and placebo for a list of adverse effects (n=20, 1 RCT, RR akathisia 2.0 CI 0.21 to 18.69, RR increased weight 3.0 CI 0.14 to 65.9, RR tremor 0.33 CI 0.04 to 2.69). When bromperidol decanoate was compared with fluphenazine depot we found no important change on global outcome (n=30, RR no clinical important improvement 1.50 CI 0.29 to 7.73). People allocated to fluphenazine decanoate and haloperidol decanoate had less relapses than those given bromperidol decanoate (n=77, RR 3.92 Cl 1.05 to 14.60, NNH 6 CI 2 to 341). People allocated bromperidol decanoate required additional antipsychotic medication somewhat more frequently than those taking fluphenazine decanoate and haloperidol decanoate but the results did not reach conventional levels of statistical significance (n=77, 2 RCTs, RR 1.72 CI 0.7 to 4.2). The use of benzodiazepine drugs was very similar in both groups (n=77, 2 RCTs, RR 1.08 CI 0.68 to 1.70). People left the bromperidol decanoate group with the same frequency as those allocated other depots (n=97, 3 RCTs, RR 1.92 CI 0.8 to 4.6). Anticholinergic adverse effects were equally common between bromperidol and other depots (n=47, RR 3.13 CI 0.7 to 14.0) and additional anticholinergic medication was needed with equal frequency in both depot groups, although results did tend to favour the bromperidol decanoate group (n=97, 3 RCTs, RR 0.80 CI 0.64 to 1.01). The incidence of movement disorders was similar in both depot groups (n=77, 2 RCTs, RR 0.74 CI 0.47 to 1.17). REVIEWERS' CONCLUSIONS: Currently, minimal poorly reported trial data suggests that bromperidol decanoate may be better than placebo injection but less valuable than fluphenazine or haloperidol decanoate. If bromperidol decanoate is available it may be a viable choice, especially when there are reasons not to use fluphenazine or haloperidol decanoate. Well-conducted and reported randomised trials are needed to inform practice in Belgium, Germany, Italy and the Netherlands.

Publication Types:
Review

PMID: 15266450 [PubMed - indexed for MEDLINE]

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7: Cochrane Database Syst Rev. 2000;(2):CD001719.Related Articles, Links
Update in:
Cochrane Database Syst Rev. 2004;(3):CD001719.

Depot bromperidol decanoate for schizophrenia.

Quraishi S, David A, Adams CE.

Department of Psychological Medicine, King College School of Medicine and Dentistry, 103 Denmark Hill, London, UK, SE5 8AF. snq@hotmail.com

BACKGROUND: Anti-psychotic drugs are the mainstay treatment for schizophrenia. Long-acting depot injections of drugs such as bromperidol decanoate are extensively used as a means of long-term maintenance treatment. OBJECTIVES: To assess the effects of depot bromperidol versus placebo, oral anti-psychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes. SEARCH STRATEGY: Relevant trials were identified by searching Biological Abstracts (1982-1999), Cochrane Library (Issue 2, 1999), Cochrane Schizophrenia Group's Register (May 1999), EMBASE (1980-1999), MEDLINE (1966-1999) and PsycLIT (1974-1999). References of all identified trials were inspected and Janssen Cilag contacted in order to identify more trials. SELECTION CRITERIA: All randomised trials focusing on people with schizophrenia where depots bromperidol, oral anti-psychotics or other depot preparations were sought. Primary outcomes were death, clinically significant change in global function, mental state, relapse, hospital admission, adverse effects and acceptability of treatment. DATA COLLECTION AND ANALYSIS: Studies were reliably selected, quality rated and data extracted. For dichotomous data Peto odds ratios (OR) with the 95% confidence intervals (CI) were estimated. The number needed to treat statistic (NNT) was to have been calculated. Analysis was by intention-to-treat. MAIN RESULTS: Four controlled clinical trials were found (total n=117). Smeraldi 1990 (n=20) compared bromperidol decanoate to placebo and found that more people in the latter group left the study by six months duration (50% versus 20%, OR 0.3 CI 0.05-7). There were no clear differences between bromperidol decanoate and placebo for a list of side effects. Ratings of global impression, mental state and needing additional antipsychotic medication all tended to favour the control depots (fluphenazine decanoate and haloperidol decanoate) and people consistently left the bromperidol decanoate group more frequently than those allocated other depots (n=97, OR 2.6 CI 0.8-9). There was no clear pattern in the occurrence of adverse effects. REVIEWER'S CONCLUSIONS: Currently, extrapolating from minimal trial data suggests that bromperidol decanoate may be better than a placebo injection but less valuable than fluphenazine or haloperidol decanoate. If bromperidol decanoate is available to the clinician it may be a viable choice, especially when there are reasons not to use fluphenazine or haloperidol decanoate. Well-conducted and reported randomised trials are urgently needed to inform practice in Belgium, Germany, Italy and the Netherlands.

Publication Types:
Review

PMID: 10796447 [PubMed - indexed for MEDLINE]

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8: Cochrane Database Syst Rev. 2000;(2):CD001717.Related Articles, Links
Update in:
Cochrane Database Syst Rev. 2005;(3):CD001717.

Depot perphenazine decanoate and enanthate for schizophrenia.

Quraishi S, David A.

Department of Psychological Medicine, Guy's, King's and St. Thomas' College School of Medicine, 103 Denmark Hill, London, UK, SE5 8AF. spjuasd@iop.kcl.ac.uk

BACKGROUND: Anti-psychotic drugs are usually given orally but compliance with medication given by this route may be difficult to quantify. The development of depot injections in the 1960s gave rise to extensive use of depots as a means of long-term maintenance treatment. Perphenazine decanoate and enanthate are depot antipsychotics that belong to the phenothiazine family and have a piperazine ethanol side chain. OBJECTIVES: To assess the effects of depot perphenazine decanoate and enanthate versus placebo, oral anti-psychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes. SEARCH STRATEGY: Biological Abstracts (1982-1998), the Cochrane Library (Issue 2, 1998), the Cochrane Schizophrenia Group's Register (June 1998), EMBASE (1980-1998), MEDLINE (1966-1998), and PsycLIT (1974-1998) were searched. References of all identified trials were also inspected for more studies and industry contacted. SELECTION CRITERIA: Randomised clinical trials focusing on people with schizophrenia where depot perphenazine decanoate and enanthate, oral anti-psychotics or other depot preparations were compared. DATA COLLECTION AND ANALYSIS: Studies were reliably selected, quality rated and data extracted. For dichotomous data Peto odds ratios (OR) with the 95% confidence intervals (CI) were estimated. Where possible, the number needed to treat statistic (NNT) was calculated. Analysis was by intention-to-treat. MAIN RESULTS: One study of six months duration, compared perphenazine enanthate to clopenthixol decanoate. There was no differences between the two for outcomes of global improvement, relapse and leaving the study early. More people in the perphenazine enanthate group required anticholinergic drugs than those allocated to clopenthixol decanoate (OR 3.6 CI 1.2-10, NNT 10). A single study (n=64, duration six weeks) compared perphenazine enanthate and its longer acting decanoate ester. Data on relapse and leaving the study early failed to show convincing differences. The enanthate group, however, experienced more movement disorders (OR 0.2 CI 0.06-0.7) than those allocated the decanoate ester of the same drug (NNT 4.0) and required more anticholinergic drugs (OR 0.2 CI 0.08-0.7, NNT 3.7). REVIEWER'S CONCLUSIONS: Depot perphenazine is in clinical use in the Nordic countries, Belgium, Portugal and the Netherlands. At a conservative estimate a quarter of a million people suffer from schizophrenia in those countries and could be treated with depot perphenazine. The total number of participants in the two trials with useful data is 236. Neither study observes the effect of oral versus depot antipsychotic drugs. Until well conducted and reported randomised trials are undertaken clinicians will be in doubt as to the effects of perphenazine depots and people with schizophrenia should exercise their own judgement or ask to be randomised.

Publication Types:
Review

PMID: 10796445 [PubMed - indexed for MEDLINE]

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9: Clin Ther. 1997 Mar-Apr;19(2):316-29.Related Articles, Links
Economic evaluation of zuclopenthixol acetate compared with injectable haloperidol in schizophrenic patients with acute psychosis.

Laurier C, Kennedy W, Lachaine J, Gariepy L, Tessier G.

Faculty of Pharmacy, University of Montréal, Canada.

Zuclopenthixol acetate is a rapid-acting, injectable neuroleptic drug with a duration of action that allows for administration once every 2 to 3 days, in contrast to injectable haloperidol, which may require administration more than once daily. To assess the place of zuclopenthixol acetate in the treatment of acute episodes of schizophrenia, a cost-consequence analysis was performed comparing this new medication with short-acting, injectable haloperidol. The perspective of the Quebec health care system was adopted. The study population comprised patients diagnosed with schizophrenia who experienced an acute episode of psychosis and who were treated with intramuscular (i.m.) haloperidol. The study assessed patients for 9 days after the start of treatment. The literature was the principal source of comparative data about the clinical outcomes of the two treatments. The total cost associated with zuclopenthixol acetate i.m. or haloperidol i.m. was modeled using a decision tree built around the number of i.m. injections required to achieve stabilization. To establish costs, expert panels were consulted and patients' files were reviewed for a sample of schizophrenic patients who had been hospitalized in a large psychiatric or general hospital subsequent to a visit to the emergency department and had received a short-acting i.m. neuroleptic drug. Only a direct medical records costs were considered. Because zuclopenthixol acetate was not on the market at the time of the study, the file review did not allow for a direct estimate of its related costs but did provide an account of haloperidol use. The literature shows that zuclopenthixol acetate is similar to haloperidol with respect to the control of psychotic episodes; however, zuclopenthixol acetate is associated with increased sedation and a lower incidence of extrapyramidal symptoms. Using the base-case estimate for the number of injections required for stabilization, the incremental cost of zuclopenthixol acetate 50 mg over haloperidol was $25.00 (1995 Canadian dollars) per patient at the psychiatric hospital and $21.00 per patient at the general hospital. The results were sensitive to the estimate of the number of injections and the number of minutes of nursing care required by agitated patients. Zuclopenthixol acetate resulted in cost savings over haloperidol if it permits a reduction of 25% in minutes of nursing care or if 85% of patients require 2 injections or less (45% requiring 1 injection and 40% requiring 2). However, whichever drug is used, the cost of the injectable neuroleptic represents a small fraction of the cost of care for acutely psychotic patients.

Publication Types:
Comparative Study
Research Support, Non-U.S. Gov't

PMID: 9152570 [PubMed - indexed for MEDLINE]

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10: Acta Psychiatr Scand. 1993 Jan;87(1):48-58.Related Articles, Links
A controlled Nordic multicentre study of zuclopenthixol acetate in oil solution, haloperidol and zuclopenthixol in the treatment of acute psychosis.

Baastrup PC, Alhfors UG, Bjerkenstedt L, Dencker SJ, Fensbo C, Gravem A, Pedersen V, Elgen K, Brekke B, Fredslund-Andersen K, et al.

KAS Nordvang, Glostrup, Denmark.

Zuclopenthixol acetate--a new injectable formulation with a duration of action of 2-3 days--was compared with conventional intramuscular and oral formulations of haloperidol and zuclopenthixol in the initial treatment of acutely disturbed, psychotic patients. The patients were stratified into 3 diagnostic categories: acute psychoses (48 patients), mania (22 patients), and exacerbation of chronic psychoses (73 patients). The patients were rated on the Brief Psychiatric Rating Scale (BPRS), the Bech-Rafaelsen Mania Rating Scale (BRMAS) (only manic patients) and globally on the Clinical Global Impression (CGI). The study was an open, randomized multicentre trial with a 6-day treatment period. The zuclopenthixol acetate patients received 1-4 doses, the haloperidol patients 1-26 and the zuclopenthixol patients 1-22 doses. The assessments on the CGI showed that all 3 treatments caused a clear reduction of the severity of illness scores in all 3 diagnostic categories, with no differences between treatments. The ratings of the acute and chronic psychotic patients on the BPRS also showed significant reductions in scores with no differences between treatments. All 3 treatments caused a rapid remission of symptoms on the BRMAS. Haloperidol induced hypokinesia in significantly more patients than zuclopenthixol acetate after 24 h. Later there were no significant differences between treatments. Zuclopenthixol acetate fulfils many desires for an amended neuroleptic formulation for the initial treatment of acutely disturbed psychotic patients.

Publication Types:
Clinical Trial
Comparative Study
Multicenter Study
Randomized Controlled Trial

PMID: 8093824 [PubMed - indexed for MEDLINE]

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11: Psychopharmacol Ser. 1988;5:62-72.Related Articles, Links
Observations on the use of depot neuroleptics in schizophrenia.

Johnson DA.

University Hospital of South Manchester, UK.

This paper reviews some of the advantages and disadvantages of long-term maintenance therapy with neuroleptics in schizophrenia. The need to separate first-illness schizophrenia from chronic schizophrenia is illustrated. The reduction in the risk of a further acute relapse with continued medication and the likely duration of maintenance therapy are discussed. The true meaning of a further relapse to the patient in terms of reduced social and work function is also discussed. The advantages of using long-acting depot injections for drug administration are stressed. The complex issue of the correct dosage for maintenance is reviewed, with no proven advantage for either very high doses or very low doses. The frequency of depressive symptoms in schizophrenia is reviewed and the possible aetiologies discussed. The decision to use short- or long-term drug therapy, and whether to use a particular method of drug administration (oral or long-acting depot injections) should be separate issues. Depot injections may, on occasions, be the appropriate method of drug administration for short-term therapies, just as oral drugs have a place in the longer-duration maintenance treatments.

Publication Types:
Review

PMID: 2901084 [PubMed - indexed for MEDLINE]

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12: Acta Psychiatr Scand. 1987 Jan;75(1):99-107.Related Articles, Links
Zuclopenthixol acetate in Viscoleo--a new drug formulation. An open Nordic multicentre study of zuclopenthixol acetate in Viscoleo in patients with acute psychoses including mania and exacerbation of chronic psychoses.

Amdisen A, Nielsen MS, Dencker SJ, Fensbo C, Ahlfors UG, Gravem A, Baastrup PC, Bjerkenstedt L, Gunby B, Wiesel FA, et al.

Eighty-three acutely disturbed, psychotic patients were included in an open multicentre study. The aim of the study was to evaluate the clinical effect of zuclopenthixol acetate in Viscoleo (CPT-A). Each patient received from one to four intramuscular injections of CPT-A during the 6-day study period. The duration of action after one injection was between 2 and 3 days and doses from 50 mg to 150 mg were sufficient for most patients. Treatment with CPT-A caused a pronounced and rapid reduction of the psychotic symptoms. At the end of the 6-day test period the mean total score on BPRS in acute non-manic and exacerbated chronic patients was reduced by more than 50 per cent. In acute manic patients the mean total score on BRMS was reduced by 57 per cent already 1 day after injection. Rapidly after the injection of CPT-A a useful short-acting sedation can be expected, but the risk for oversedation even after a second injection is low. The frequency of unwanted effects, including extrapyramidal reactions, was low and the severity of symptoms was most often mild. With a rapid onset of action, a duration of effect of 2 to 3 days, and few and mild side effects, CPT-A offers advantages over the neuroleptic preparations conventionally used in the initial treatment of acutely disturbed, psychotic patients.

Publication Types:
Clinical Trial

PMID: 2883816 [PubMed - indexed for MEDLINE]

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13: Curr Med Res Opin. 1986;10(5):326-9.Related Articles, Links
Pipothiazine palmitate: a versatile, sustained-action neuroleptic in psychiatric practice.

Schmidt K.

A study lasting 1 year assessed the effectiveness and tolerance of depot neuroleptic treatment with pipothiazine palmitate in 52 patients suffering from schizophrenia or related conditions (17 acute and 35 chronic). A 100 mg dose was given to 31 patients and 50 mg to 21 patients: 40 patients received injections 4-weekly, 8 patients 3-weekly and 4 patients 2-weekly. Duration of treatment ranged from 3 to 12 months, involving a total of 347 patient-months. The significant improvement produced by pipothiazine palmitate as shown by patient assessment, based on the Parkside Behaviour Rating Scale (p less than 0.05), a Hamilton-based affect scale (p less than 0.05) and a global rating scale of affect and psychomotor activity (p less than 0.01). Most target symptoms were relieved. A particularly favourable affective response was noted. The incidence of adverse reactions was low and did not present major problems; 6 cases of dystonic reaction were seen, but dealt with promptly and effectively.

PMID: 2880694 [PubMed - indexed for MEDLINE]

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14: Psychopharmacology (Berl). 1986;90(3):412-6.Related Articles, Links
Serum concentrations and clinical effect of zuclopenthixol in acutely disturbed, psychotic patients treated with zuclopenthixol acetate in Viscoleo.

Amdisen A, Aaes-Jørgensen T, Thomsen NJ, Madsen VT, Nielsen MS.

Zuclopenthixol acetate, 5%, in Viscoleo was administered IM to 19 acutely disturbed, psychotic patients in doses of 50-150 mg. Fifteen patients received one injection, whereas four of the patients had two or three injections, usually with intervals of 3 days. The zuclopenthixol concentrations in serum were measured in series of samples taken from each patient during a 3-day period following the injection. In patients given identical doses serum concentrations of about the same order were obtained. Significant and good correlations were found between dose and maximal serum concentration and between dose and area under the serum concentration curve. The average serum concentration curve obtained when adjusting the data to a 100 mg dose has a maximum of 41 ng/ml after about 36 h, decreasing to 15 ng/ml after 72 h. A dose of 50-150 mg zuclopenthixol acetate in Viscoleo appeared to be sufficient for controlling the symptoms for most acutely disturbed, psychotic patients. The frequency of side effects, including extrapyramidal reactions, was low and the adverse reactions mostly mild, indicating that the risks for severe complications generally might be minimal. With a rapid onset of action, few and mild side effects, good tolerability at the injection site, and a duration of effect of 2-3 days, zuclopenthixol acetate in Viscoleo appears to offer advantages compared to conventional neuroleptic treatment in patients in whom an acute, calming effect is desired.

PMID: 2878462 [PubMed - indexed for MEDLINE]

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15: J Clin Psychiatry. 1984 May;45(5 Pt 2):13-21.Related Articles, Links
Observations on the use of long-acting depot neuroleptic injections in the maintenance therapy of schizophrenia.

Johnson DA.

The advantages of both long-acting injections and oral administration of neuroleptic agents in treating schizophrenia are discussed. Problems related to patient noncompliance and other factors relevant in evaluating long-term maintenance therapy are considered, as well as variables that influence the duration of maintenance therapy. The results of discontinuation, whether initiated by patient or physician, are discussed, along with the limitations of long-term medication therapy (e.g., depression, dyskinesia, extrapyramidal symptoms). General guidelines are provided for evaluating dose requirements in maintenance therapy.

Publication Types:
Clinical Trial
Review

PMID: 6143743 [PubMed - indexed for MEDLINE]

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16: J Clin Psychiatry. 1983 Jun;44(6 Pt 2):3-6.Related Articles, Links
Problems of compliance in the outpatient treatment of schizophrenia.

Kane JM.

The importance of treatment compliance in the outpatient care of schizophrenia is discussed, and research on this problem and on various approaches to its solution is reviewed briefly. The role of injectable medication in increasing adherence to treatment in the outpatient setting is important, although studies in this area have suffered from problems of inadequate duration and sample size, and differing definitions of relapse. Whatever treatment is chosen, careful attention to side effects, which may be mild or subclinical, is essential. The psychological meanings attached by patients to their illness and its treatment are also important considerations, as is education of patients and professionals on issues related to treatment adherence.

PMID: 6133854 [PubMed - indexed for MEDLINE]

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17: Pharmacology. 1982;24(3):147-55.Related Articles, Links
Catalepsy produced by long-acting neuroleptics, fluphenazine enanthate and fluphenazine decanoate, in mice.

Yamada K, Furukawa T.

The cataleptic state induced by the depot-type preparations of fluphenazine (FZ) was investigated in mice. Intramuscular injections of FZ-enanthate or FZ-decanoate produced a marked and long-lasting catalepsy, which was antagonized by trihexyphenidyl, biperiden and promethazine but not by l-dopa. These anticataleptic effects disappeared after several hours and catalepsy occurred again. The cataleptic effects of FZ-enanthate and FZ-decanoate were increased by (D-Ala2, MePhe4, Met(0)5-ol)-enkephalin, aminooxyacetic acid and haloperidol. The results indicate that the cataleptic effects of FZ-enanthate and FZ-decanoate correspond with their long duration of antipsychotic effects and that the catalepsy may involve enkephalinergic, GABAergic and cholinergic as well as dopaminergic neuron activity.

Publication Types:
Research Support, Non-U.S. Gov't

PMID: 7200248 [PubMed - indexed for MEDLINE]

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18: Acta Psychiatr Belg. 1981 Mar-Apr;81(2):182-8.Related Articles, Links
Experience with depot neuroleptics in ambulatory practice.

Fiolet J.

Over the years, the depot neuroleptics clopenthixol decanoate, flupentixol decanoate, fluphenazine decanoate and pipotiazine palmitate have prove their excellent tolerance: testing the sensitivity of the patient with the corresponding oral neuroleptic or with a low dose of the injectable form is no more necessary, operative anaesthesia is no more feared. Side-effects are largely due to the fact that the drug is actually taken, as opposed to oral treatments; they consist mainly of drowsiness or tiredness, and of extrapyramidal symptoms (preferably controlled by dexetimide, because of its long duration of action). Among the advantages of depot treatments, the author mentions an increasing motivation to accept medication, because of the reduction of hospitalisations and the fact that the patient is not reminded "three times daily" of his "ill state". Among the disadvantages, he mentions the fear of injection (the alternative being long-acting oral penfluridol), depression (esp. with fluphenazine decanoate) and the fact that the absorption cannot be interrupted in a short time.

PMID: 6117188 [PubMed - indexed for MEDLINE]

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19: Acta Psychiatr Belg. 1981 Mar-Apr;81(2):173-81.Related Articles, Links
The use of long-acting neuroleptics in the acute psychoses.

Cassano GB, Placidi GF.

Out of 120 inpatients treated with long-acting neuroleptics (LANs) between May 1977 and May 1978, the authors have selected 43 patients with clear-cut acute psychotic symptoms and high doses or frequent injections of fluphenazine decanoate: 19 schizophrenics, 13 schizoaffective psychoses and 11 manics. The average single dosage was 32 to 37 mg depending on the diagnostic category; the average weekly dosage was 45 to 55 mg; the average frequency of injections was one every 5 to 7 days. Drug combinations could be greater reduced. On discharge, all long-acting treatments were discontinued in manics, against some 60% of schizophrenics and schizoaffective psychoses. Among the advantages of LANs, the authors mention optimum pharmacokinetics (hence, lower doses), increased compliance from the part of the patient (less hostility thanks to decreased administrations than with oral medications), avoidance of cases of intestinal malabsorption, lowered financial burden (less treatment units, fewer admissions, shorter duration of hospitalization, less polypharmacy.

PMID: 6117187 [PubMed - indexed for MEDLINE]

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20: Acta Psychiatr Belg. 1981 Mar-Apr;81(2):161-72.Related Articles, Links
Long-term maintenance treatment in chronic schizophrenia. Some observations on outcome and duration.

Johnson DA.

The authors reports on several studies of his own, namely two discontinuation studies and a survey of all known schizophrenic patients in a defined catchment area for a period of two years. Of the 140 patients prescribed a long-acting neuroleptic (LAN), 83% were still receiving injections after 2 years. Some 70% were responders, but 50% were rated on the lowest point of social functioning on a relative's scale. The discontinuation studies followed up patients for up to 4 years after discontinuing LAN. For a first schizophrenic illness the highest relapse rate is in the first year (29%), but thereafter (2-4 years it remains fairly constant (3-6%), which points to the need for more long term studies. Patients who had received depot therapy for a minimum of 1 year have a better survival rate than patients discontinuing LAN after a shorter period. For chronic schizophrenia the highest relapse rate is in the first year (60%), but falls each year over the next three years (11% in the second year, 5% in 2-4 years). There is no difference of outcome with increased duration of medication within the four year periods on medication studied. The adoption of LANs in the United Kingdom over the past 13 years is in the author's opinion the most important single improvement in the treatment of schizophrenia; but in the absence of any clear indication that LANs can be discontinued after even 4 years, the emphasis must remain on their proper use: personalised prescriptions (dose reduced with time down to the lowest possible dosage) and caution against unnecessary polypharmacy.

PMID: 6117186 [PubMed - indexed for MEDLINE]