Maintenance Therapy In Schizophrenia Research Articles

Use of the Third-Generation Atypical Antipsychotic Aripiprazole (Zylaxera®) for Treatment of Depressive States in Schizophrenia: Efficacy and Safety Study

Background: Aripiprazole, among other atypical antipsychotics, is recommended as a drug for maintenance therapy in schizophrenia in cases in which the patient is identified as having depressive symptoms. At the same time, depression in schizophrenia is not listed as a separate indication for Aripiprazole, its antidepressant properties are considered only in the recommendations for the treatment of bipolar depression and augmentation of antidepressant therapy in recurrent depressive disorder. There are no works characterizing the efficacy of the drug in depression in patients with schizophrenia, as well as evaluating the spectrum of its antidepressant action in such conditions.Objective of the study: to examine the therapeutic efficacy and safety of Aripiprazole (Zylaxera®) in the augmentation therapy of moderate to severe depressive states in patients with schizophrenia.Patients and methods: the efficacy and safety of Aripiprazole (Zylaxera®) augmentation therapy with 5–20 mg daily dose for 6 weeks was studied in 72 patients aged 18 to 47 years (all women) with depressive states of at least 17 Hamilton Scale scores in remitted schizophrenia, postchizophrenic depression and schizotypal disorder (F20.01 + F32.1–2; F20.04; F21.3–4 + F32.1–2). The HDRS-21, CGI, and UKU scales were used for psychometric assessment.Results: the effectiveness of augmentation of antidepressant therapy with Zylaxera® was revealed in the majority of patients: the rate of responders as evaluated by the HDRS-21 scale (reduction of severity of depressive disorders by 50% or more) was 67.2% and 71.4% for the CGI scale. At the same time, it was established that the group of responders had a certain similarity in terms of psychopathological structure of depressive states.Conclusion: it has been established, that in patients suffering from schizophrenia Zylaxera® has a distinct efficacy in augmentation of antidepressant therapy and has a favorable tolerability profile. The maximum efficacy of the drug within the framework of such use is observed in depressive states with predominance of negative affectivity.

The Novel Antipsychotic Drug Cariprazine and Cognition Enhancing Drugs: Indications for their Use as the Add-on Therapy in Schizophrenia.

Schizophrenia and schizoaffective disorder are treated with antipsychotic drugs. Some patients show treatment-resistant forms of psychotic disorders, and in this case, they can be treated with clozapine. Based on the previous reviews on novel antipsychotic drugs, it is important to know whether the add-on therapy with the new drugs can ameliorate the positive and negative schizophrenic scale (PANSS) total score. The aim of this review is to suggest an appropriate treatment for patients with treatment-resistant forms of psychotic disorders. A combination of the currently available antipsychotic drugs with novel antipsychotic or modulating drugs might improve negative schizophrenic symptoms and cognitive function and thereby social functioning and quality of life. The mechanisms of action, the therapeutic effects, and the pharmacokinetic profiles of novel antipsychotic drugs such as cariprazine, brexipiprazole, and lumateperone have been updated. Published case reports of patients with treatment-resistant psychoses have also been discussed in this study. These patients were treated only with clozapine, as a result of which a high PANSS total score was observed. Only the add-on therapy with cariprazine improved the score, and above all, the negative schizophrenic symptoms and cognitive functions were improved. For the ensurance of a constant antipsychotic drug concentration, long-acting injectable antipsychotic drugs might be a choice for the maintenance therapy in schizophrenia. New modulating drugs, such as receptor positive allosteric modulators (N-methyl-D-aspartate receptor; subtype 5 of the metabotropic glutamatergic receptor) and encenicline, an alpha7 nicotinic cholinergic receptor agonist, have been investigated in preclinical and clinical trials. In clinical trials, patients with treatment-resistant forms of psychosis should be examined to know whether combination therapy with clozapine and a novel antipsychotic drug can ameliorate the PANSS total score. In schizophrenia, long-acting injectable antipsychotic drugs are safe and tolerable maintenance therapy. In further clinical studies, it should be investigated whether patients with treatment-resistant forms of psychoses can improve negative schizophrenic symptoms and cognitive functions by the add-on therapy with cognitionenhancing drugs.

A Case of Extrapyramidal Symptoms Secondary to Long-Acting Injectable Paliperidone Palmitate

Paliperidone palmitate is a long-acting injectable formulation of the atypical antipsychotic paliperidone. The once-monthly injection is approved for acute and maintenance therapy of schizophrenia in adults. Extrapyramidal symptoms are a known adverse effect of antipsychotics; incidence rates of EPS with PP are up to 18%. Given its longer half-life and steady blood levels, PP-induced EPS can cause a sustained and serious functional impairment of several months’ duration, significantly impacting the quality of life.

Combined study of genetic and epigenetic biomarker risperidone treatment efficacy in Chinese Han schizophrenia patients

Nowadays, risperidone is an atypical antipsychotic drug that has been increasingly used for treatment and maintenance therapy in schizophrenia. However, partially affected by genetic or environmental factors, there is significant difference in treatment outcomes among patients. In this study, we aimed to interpret the difference between good and poor responders treated with risperidone in both genetic and epigenetic levels in 288 mainland Chinese patients. We recruited a Henan cohort including 98 patients as initial discovery group and then confirmed our results in Shanghai cohort. In genetic studies, we found 10 candidate single-nucleotide polymorphisms (SNPs) and 2 rare variants in Henan cohort by next-generation sequencing of 100 risperidone-response-related genes. After replication in Shanghai cohort by massarray platform, ultimately, rs6706232 and rs4818 were significantly associated with risperidone response in the two cohort meta-analysis (P=0.024 and 0.04, respectively). Besides, we also selected another reported 17 candidate SNPs associated with risperidone drug response to replicate in our mainland Chinese samples, while, we found no significant SNPs after Bonferroni correction. In epigenetic studies, we investigated the methylation status in promoters or gene-coding region of risperidone drug response-related genes including CYP3A4, CYP2D6, ABCB1, HTR2A, DRD2. Totally we found seven significant CpG sites in the meta-analysis with Bonferroni-corrected PCYP3A4_CpG_-36=0.0014, PCYP3A4_CpG_-258=0.0013, PCYP3A4_CpG_-296=0.0014, PCYP3A4_CpG_-367:-372:-374=0.028, PCYP2D6_CpG_193=0.012, PCYP2D6_CpG_242:244:250=0.00076 and PCYP2D6_CpG_284=0.034, respectively. As genetic and epigenetic factors may interactively affect drug response, we finally carried out a multivariant interaction analysis with multifactor dimensionality reduction and discovered a significant four-locus model (CYP3A4_CpG_-82:-86 +rs6280+rs1800497+rs6265, P=0.038) affecting drug response. These findings could partially explain different risperidone response outcome in Chinese population in a systematic level.

“Long-acting” olanzapine in maintenance therapy of schizophrenia: A study with plasma levels

Introduction. This prospective study was performed to evaluate clinical efficacy and tolerability of olanzapine long-acting injection (OLZ-LAI) and the relation between OLZ plasma level (PL) and the clinical outcome in maintenance therapy of schizophrenia. Material and methods. Twenty-five chronic schizophrenic outpatients with age ranging from 18 to 65 years were included in this 9-month study. Patients were given a dosage of either 210 or 300 or 405 mg of OLZ-LAI every 28 days. Patients were evaluated at baseline and every four weeks by Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Symptom Scale (PANSS); at the same time, PL of OLZ was determined. The metabolic profile (aspartate aminotransferase, alanine aminotransferase, high-density lipoprotein, low-density lipoprotein, total cholesterol, and glucose levels) was analyzed every two months. Results. BPRS and total PANSS showed a statistically significant improvement from T2 with a clinical stabilization of psychopathological picture. PL ranged from 4.0 to 78.9 ng/ml (mean 20.59 ng/ml ± 14.66 standard deviation). The coefficient of variation of PLs was related to clinical stabilization. No post-injection delirium sedation syndrome occurred. Conclusions. Our data reveal the efficacy of OLZ-LAI in maintenance treatment of schizophrenia at lower dosages also in comparison with that of oral therapy. OLZ-LAI seems to be useful for guaranteeing constant PL of the drug. A lesser variation of PL was the most predictable factor associated with maintenance of clinical benefit.

Once-monthly paliperidone injection for the treatment of schizophrenia

Paliperidone palmitate is a new long-acting antipsychotic injection for the treatment of acute and maintenance therapy in schizophrenia. Paliperidone (9-hydroxyrisperidone) is the major active metabolite of risperidone and acts at dopamine D2 and serotonin 5HT2A receptors. As with other atypical antipsychotics, it exhibits a high 5HT2A:D2 affinity ratio. It also has binding activity as an antagonist at α1-and α2 adrenergic receptors and H1 histaminergic receptors, but has virtually no affinity for cholinergic receptors. Paliperidone palmitate has been shown to be effective in reducing Positive and Negative Syndrome Scale total scores in four short-term trials in acute schizophrenia. It was also effective as maintenance therapy in a long-term trial in which time to recurrence of symptoms was significantly longer in paliperidone-treated patients compared with placebo. In addition, paliperidone was shown to be noninferior to risperidone long-acting injection in one study, but this noninferiority was not established in another longer study comparing the two drugs. Treatment should be initiated with 234 mg on day 1 and 156 mg on day 8, followed by a recommended monthly maintenance dose of 39–234 mg based on efficacy and tolerability. Paliperidone palmitate is generally well tolerated, although it can cause weight gain and a rise in prolactin levels, which is generally greater in women than in men. Overall, paliperidone palmitate may have advantages over other currently available long-acting injections, and therefore may be a useful alternative for the treatment of schizophrenia, although further long-term trials comparing it with active treatments are warranted.

Clozapine maintenance therapy in schizophrenia

Long-term pharmacotherapy with antipsychotic agents is an important aspect of the management of schizophrenia. In patients responsive to the chosen treatment, maintenance therapy is usually conducted by halving the drug dose that has proven effective during the acute phase. This strategy is suitable for maintaining remission; moreover, it can improve the patients' quality of life. Records from over 1000 patients treated with clozapine during the past 22 years were examined; 782 of these patients were diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision (DSM-IV-TR) criteria (with the modification in early years). From this group, 181 patients were treated with clozapine for at least a year. The mean duration of long-term maintenance treatment with clozapine was 12.2±4.25 years (range: from 14.5 months to 18 years). Clozapine was administered in a daily dose of 50–200 mg (mean: 71.5±14.12 mg). In 76 schizophrenics, treatment was initiated with clozapine, whereas 105 patients were switched over from other treatments after their failure. The control group comprised 152 patients on long-term maintenance therapy with haloperidol. Clozapine administered for long-term maintenance therapy was effective both in paranoid and in catatonic schizophrenia. It also accomplished good results in patients with disorganized or residual schizophrenia, as well as in individuals with schizoaffective psychosis. Relapse rate was similar to that observed in the haloperidol group; however, patient compliance, side-effect profile, and therapeutic efficacy were all superior in the clozapine group. Long-term maintenance therapy with clozapine is successful. Compliance is good; schizophrenic patients are willing to take this atypical antipsychotic for years on end. Clozapine treatment is associated with a low relapse rate and a favorable safety profile.

Maintenance therapy in schizophrenia: a critical comment.

The paper's aim was to evaluate a rationale for maintenance therapy in schizophrenia and to consider the feasibility of intermittent targeted therapy as an alternative treatment strategy. This was achieved by a selected review of the relevant English-language literature published since 1966 through a Medline search and cross-referencing. Current scientific evidence for continuous maintenance therapy in schizophrenia was found equivocal as the randomization in clinical trials lumped together heterogeneous groups of patients, thereby creating a wide gap between research and clinical practice. In addition, the majority of studies took a narrow view of the concept of relapse. For these reasons, targeted intermittent treatment was probably prematurely discarded altogether. The rationale for use and optimal duration of maintenance antipsychotic pharmacotherapy for schizophrenia has not been adequately validated. The construct validity of outcome indicators currently used in maintenance treatment studies in schizophrenia should be reconsidered. Intermittent targeted treatment may represent a viable option in some clinical situations and warrant further evaluation. With the widespread use of atypical antipsychotics, current long-term maintenance strategies may need a reappraisal.

Standard olanzapine versus placebo and ineffective-dose olanzapine in the maintenance treatment of schizophrenia

Two studies compared the efficacy of standard-dose oral olanzapine (5 to 15 mg a day) with placebo and with ineffective-dose olanzapine (1 mg a day) in maintenance therapy of schizophrenia. The studies were 46-week double-blind extensions of multicenter studies that assessed the efficacy of olanzapine in the acute treatment of schizophrenia. Subjects were 120 adults who met DSM-III-R criteria for schizophrenia with an acute exacerbation and who had a minimum score of 24 on the Brief Psychiatric Rating Scale, who had responded to acute therapy (defined as at least a 40 percent reduction in the BPRS score from baseline or a score of 18 or less during up to six weeks of treatment), and who were outpatients at their last acute-phase visit. Relapse was defined as hospitalization for psychopathology. Relapse risk was analyzed using Kaplan-Meier survival analysis and life table analysis. Patients who relapsed were discontinued from the studies. In the first study (N = 58), patients in the standard-dose olanzapine group experienced a significantly lower relapse risk (p = .002) over one year than patients treated with placebo. The estimated one-year risk of relapse with olanzapine was 28.6 percent, compared with 69.9 percent with placebo. Results were similar in the second study (N = 62); patients treated with standard-dose olanzapine had a significantly reduced risk of relapse (p = .018) over one year compared with patients treated with ineffective-dose olanzapine. The estimated one-year risks of relapse were 19.6 percent for standard-dose olanzapine and 45.5 percent for ineffective-dose olanzapine. Olanzapine is superior to placebo and ineffective-dose olanzapine in the maintenance therapy of schizophrenia.

Professional attitudes in the UK towards neuroleptic maintenance therapy in schizophrenia

Controlled trials show that about 80% of schizophrenic patients remain relapse free when given adequate neuroleptic maintenance therapy but this level of efficacy is not achieved in clinical practice. Guidelines for proper use of neuroleptics in relapse prevention were developed by a group of experienced psychiatrists – the ‘Consensus Group’ – in 1989. In this survey, the views of UK psychiatrists, GPs, CPNs and pharmacists involved in community care of schizophrenia were compared with the Guidelines.

Fluphenazine decanoate in acute and maintenance therapy of schizophrenia

1. 1. The knowledge of the pharmacokinetic profile of fluphenazine decanoate (FPZ-D) suggested it was suitable for treatment of schizophrenic patients not just during the maintenance phase of the disease but also during acute relapses. 2. 2. 27 acute schizophrenic in-patients (diagnosed according to the DSK III) were treated with FPZ-D, 25 mg i.m. with repeated administrations (after 2, 4, 30 days). 3. 3. FPZ-D proved effective in all cases, already after the second day and particularly on Brief Psychiatric Rating Scale items such as delusion, hallucinations, hostility. 4. 4. Extrapyramidal side-effects, appeared in about 40% of the patients. 5. 5. The use of the drug both in the acute phase and maintenance schizophrenia therapy is envisaged, overcoming the problems deriving from the rejection by patients of any therapeutic tool and consequently the therapeutic “milieu”.

Approaches to Maintenance Therapy in Schizophrenia

Approaches to Maintenance Therapy in Schizophrenia

Further Observations on the Duration of Depot Neuroleptic Maintenance Therapy in Schizophrenia

SummaryTwo patient samples, with different criteria for selection, have been surveyed following maintenance therapy discontinuation. The patients had previously remained in a steady mental state on depot injections for periods varying between one and four years. Both the rates of relapse and pattern of relapse suggest that patients responding to medication need to remain on maintenance therapy for a minimum of four years. The results further suggest that in chronic schizophrenia the drugs only suppress symptoms and that the prognosis following discontinuation is substantially unchanged by increased duration of medication, even after four years. The possibility of using short-term ‘drug holidays’ to reduce the risk of unwanted effects was explored; after only three months without drugs, the risks of relapse were significantly increased.

Assessment of drugs in schizophrenia. Assessment of psychiatric and social state. 20V

British Journal of Clinical PharmacologyVolume 3, Issue S2 p. 385-390 Free Access Assessment of drugs in schizophrenia. Assessment of psychiatric and social state. 20V DB Scott, DB ScottSearch for more papers by this authorFP Buckley, FP BuckleySearch for more papers by this authorGB Drummond, GB DrummondSearch for more papers by this authorDG Littlewoods, DG LittlewoodsSearch for more papers by this authorWR Macrae, WR MacraeSearch for more papers by this author DB Scott, DB ScottSearch for more papers by this authorFP Buckley, FP BuckleySearch for more papers by this authorGB Drummond, GB DrummondSearch for more papers by this authorDG Littlewoods, DG LittlewoodsSearch for more papers by this authorWR Macrae, WR MacraeSearch for more papers by this author First published: June 1976 https://doi.org/10.1111/j.1365-2125.1976.tb03730.xCitations: 10AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat References Birley, J.L.T. & Brown, G.W. (1970). Crises and life changes preceding the onset or relapse of schizophrenia. Br. J. Psychiat., 116, 327– 333. Brown, G.W. & Birley, J.L.T. (1968). Crises and life changes and the onset of schizophrenia. Hlth. soc. Behav., 9, 203– 214. Brown, G.W., Birley, J.L.T. & Wing, J.K. (1972). Influence of family life on the course of schizophrenic disorders: a replication. Br. J. Psychiat., 121, 241– 258. Brown, G.W. & Rutter, M.L. (1966). The measurement of family activities and relationships. Hum. Relat., 19, 241– 263. Cooper, J.E. et al. (1972). Psychiatric Diagnosis in New York and London. Maudsley Monograph No. 20. London: Oxford University. Dencker, S.J., Frankenberg, K., Malm, U. & Zell, B. (1973). A controlled one-year study of pipothiazine palmitate and fluphenazine decanoate in chronic schizophrenic syndromes. Acta psychiat. scand., suppl., 241, 101– 118. Hirsch, S.R., Gaind, R., Rohde, P.D., Stevens, B.C. & Wing, J.K. (1973). Out-patient maintenance of chronic schizophrenic patients with long-acting fluphenazine: a double-blind placebo trial. Br. med. J., 1, 633– 637. Leff, J.P., Hirsch, S.R., Gaind, R., Rohde, P.D. & Stevens, B.C. (1973). Life-events and maintenance therapy in schizophrenic relapse. Br. J. Psychiat., 123, 659– 660. Leff, J.P. & Vaughn, C. (1972). Psychiatric patients in contact and out of contact with services. In Evaluating a Community Psychiatric Service, ed. J.K. Wing & A. Hailey London: Oxford University. Leff, J.P. & Wing, J.K. (1971). Trial of maintenance therapy in schizophrenia. Br. med. J., 3, 599– 604. Maxwell, A.E. (1972). Difficulties in a dimensional description of symptomatology. Br. J. Psychiat., 121, 19– 26. Sillitoe, K.K. (1969). Planning for Leisure. Government Social Survey. London: HMSO. Vaughn, C. & Leff, J.P. (in press). The measurement of expressed emotion in families of psychiatric patients. Br. J. soc. clin. Psychol.. Wing, J.K., Cooper, J.E. & Sartorius, N. (1974). The Measurement and Classification of Psychiatric Symptoms. London: Cambridge University. World Health Organization (1973). The International Pilot Study of Schizophrenia, 1. Geneva: WHO. Citing Literature Volume3, IssueS2June 1976Pages 385-390 ReferencesRelatedInformation

Long‐term follow‐up studies of drugs in schizophrenia.

British Journal of Clinical PharmacologyVolume 3, Issue S2 p. 411-415 Free Access Long-term follow-up studies of drugs in schizophrenia. NW Imlah, NW ImlahSearch for more papers by this author NW Imlah, NW ImlahSearch for more papers by this author First published: June 1976 https://doi.org/10.1111/j.1365-2125.1976.tb03735.xCitations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL References Keskiner, A. (1973). A long term follow up of fluphenazine enanthate treatment. Curr. ther. Res., 15, 305. Lancet (1974). Rauwolfia derivatives and cancer. Lancet, 2, 701– 702. Lancet (1975). Rauwolfia and breast cancer. Lancet, 2, 312– 313. Leff, J.P. & Wing, J.K. (1971). Trial of maintenance therapy in schizophrenia. Br. med. J., 3, 599– 604. Mathalone, M.B.R. (1966). Ocular complications of phenothiazine. Trans. Ophthal. Soc. U.K., 86, 77. Overall, J.E. & Gorham, D.R. (1962). The Brief Psychiatric Rating Scale. Psychological Reports, 10, 799– 812. Wilson, D.J. (1969). Ocular changes due to phenothiazine derivatives—a survey. Trans. Ophthal. Soc. U.K., 86, 963. Wing, J.K., Birley, J.L.T., Cooper, J.E., Graham, P. & Isaacs, A.D. (1967). Reliability of a procedure for measuring and classifying present psychiatric state. Br. J. Psychiat., 113, 499– 515. Citing Literature Volume3, IssueS2June 1976Pages 411-415 ReferencesRelatedInformation

Observations on the dose regime of fluphenazine decanoate in maintenance therapy ofschizophrenia.

An analysis of the drug regimes prescribed to two separate groups of unselected schizophrenic patients indicates certain trends of clinical importance. The results demonstrate a need for the adoption of a personalized dose regime. The scatter of dose regimes found effective is too great to recommend a standardized approach to the prescription of L.A.P. injections. Two other results of particular significance are that the dose of drug required to control symptoms can be gradually reduced in nearly half of patients,and that helpful trends in prescribing were identified that will help the clinician to abolish side-effects.