Idazoxan and Response to Typical Neuroleptics in Treatment-Resistant Schizophrenia

1996 ◽  
Vol 168 (5) ◽  
pp. 571-579 ◽  
Author(s):  
Robert E. Litman ◽  
Tung-Ping Su ◽  
William Z. Potter ◽  
Walter W. Hong ◽  
David Pickar
Keyword(s):  
Negative Symptoms ◽  
Rating Scale ◽  
Random Order ◽  
Symptom Improvement ◽  
Treatment Resistant ◽  
Neuroleptic Treatment ◽  
Double Blind ◽  
Clozapine Treatment ◽  
Psychiatric Rating Scale ◽  
Typical Neuroleptics

BackgroundWe investigated whether antagonism of α2adrenergic receptors would augment treatment response in schizophrenia, by administering idazoxan, an α2antagonist drug, to treatment-resistant patients on typical neuroleptics.MethodSeventeen hospitalised treatment-resistant patients with DSM–III–R schizophrenia or schizoaffective disorder were studied on typical neuroleptic treatment, on treatment with idazoxan plus typical neuroleptic, and after discontinuation of idazoxan, in fixed, non-random order, and under double-blind, placebo-controlled conditions.ResultsThe addition of idazoxan to fluphenazine treatment resulted in significant reductions of global psychosis and total, positive and negative symptoms on the Brief Psychiatric Rating Scale, compared to neuroleptic treatment alone. Symptom improvement significantly correlated with idazoxan-induced changes in indices of noradrenergic function. In a subgroup of patients, idazoxan plus typical neuroleptic treatment compared favourably with clozapine treatment, when both were compared to typical neuroleptic treatment alone.ConclusionsThe antagonism of α2receptors augmented therapeutic response to typical neuroleptic treatment in treatment-resistant patients with schizophrenia. This antagonism may contribute to clozapine's superior antipsychotic effects.

Sulpiride augmentation in people with schizophrenia partially responsive to clozapine

1997 ◽  
Vol 171 (6) ◽  
pp. 569-573 ◽  
Author(s):  
Roni Shiloh ◽  
Zvi Zemishlany ◽  
Dov Aizenberg ◽  
Marguerite Radwan ◽  
Bruria Schwartz ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Rating Scale ◽  
Clinical Status ◽  
Chronic Schizophrenia ◽  
Current Treatment ◽  
Psychotic Symptoms ◽  
Double Blind ◽  
Clozapine Treatment ◽  
Psychiatric Rating ◽  
Psychiatric Rating Scale

BackgroundWe hypothesised that a combined regimen of clozapine, a relatively weak D2-dopaminergic antagonist, and sulpiride, a selective D2 blocker, would demonstrate a greater antipsychotic efficacy by enhancing the D2 blockade of clozapine.MethodTwenty-eight people with schizophrenia, previously unresponsive to typical antipsychotics and only partially responsive to current treatment with clozapine, received, double-blind, 600 mg/day sulpiride or placebo, in addition to an ongoing clozapine treatment. The clinical status was evaluated before, during, and at the end of 10 weeks of sulpiride addition using the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms, and Hamilton Rating Scale for Depression.ResultsThe clozapine–sulpiride group exhibited substantially greater and significant improvements in positive and negative psychotic symptoms. About half of them, characterised by a younger age and lower baseline SAPS scores, had a mean reduction of 42.4 and 50.4% in their BPRS and SAPS scores, respectively.ConclusionsA subgroup of patients with chronic schizophrenia may substantially benefit from sulpiride addition to clozapine.

Clozapine augmented with risperidone in treatment-resistant schizophrenia

2017 ◽  
Vol 41 (S1) ◽  
pp. S385-S385 ◽  
Author(s):  
G. Sulejmanpasic ◽  
S. Bise
Keyword(s):  
Negative Symptoms ◽  
Rating Scale ◽  
Positive Symptom ◽  
Treatment Resistant ◽  
Double Blind ◽  
Dopamine And Serotonin Receptors ◽  
Competing Interest ◽  
Psychiatric Rating Scale ◽  
Additional Clinical Benefit ◽  
Risperidone Treatment

IntroductionThe evolution of various pharmacological therapies for schizophrenia has given rise to several pharmacological models for the neuroreceptor targets of antipsychotics and the influence of various neuroreceptors on specific symptoms and side effects.ObjectivesExperience in clinical practice affirms clozapine's position as the treatment of choice for patients with treatment-refractory schizophrenia. Unlike clozapine, risperidone has a more targeted profile of neurotransmitter binding, with particular predilection for dopamine and serotonin receptors. Risperidone is, to date, the most extensively documented clozapine augmentation agent.AimThe aim was to evaluate clinical efficacy, safety and tolerability of augmenting clozapine with risperidone in patients with treatment-resistant schizophrenia.MethodsIn a randomized, double-blind, placebo-controlled 8-week trial, 10 patients unresponsive or partially responsive to 300 mg/day of clozapine monotherapy (n = 5) received a steady dose of 450 mg/day clozapine combined with or up to 4 mg/day of risperidone (n = 5). Patient psychopathology was assessed at 2-week intervals with the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS) and Clinical Global Impression (CGI) improvement scale.ResultsFrom baseline to week 4 and week 8, mean BPRS total and positive symptom subscale scores were reduced significantly in both groups, but the reductions were significantly greater with clozapine/risperidone treatment. Reductions in SANS scores were also significantly greater with clozapine/risperidone treatment than with clozapine monotherapy group. Clozapine/risperidone treatment did not induce additional weight gain or agranulocytosis compared with clozapine monotherapy treatment.ConclusionsClozapine augmentation with risperidone appears to be well tolerated, safe and may provide additional clinical benefit for patients who are nonresponsive or only partially responsive to clozapine alone.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Clozapine in treatment-resistant schizophrenic patients: preliminary results from an open prospective study

1996 ◽  
Vol 13 (1) ◽  
pp. 13-18
Author(s):  
Isabelle Jalenques ◽  
Eliane Albuisson ◽  
Igor Tauveron
Keyword(s):  
Prospective Study ◽  
Negative Symptoms ◽  
Rating Scale ◽  
Health Care Utilisation ◽  
Positive Symptoms ◽  
Treatment Resistant ◽  
Beneficial Effects ◽  
Clozapine Treatment ◽  
Schizophrenic Patients ◽  
Open Prospective Study

AbstractObjective:This report describes an open prospective study of the effects of clozapine on positive and negative symptomatology in treatment resistant schizophrenic patients.Method:In this prospective study, 15 DSM-III-R schizophrenic patients, who had failed to respond to various neuroleptics were followed up for a period of 21 months (median: 9; 25th and 75th percentiles: 4-10). When clozapine treatment was initiated, the mean duration of the illness was 16 +/-9 years. Brief Psychiatric Rating Scale (BPRS) scores, BPRS ‘positive symptoms’ and BPRS ‘anergia factor’ scores were all rated at days 0 and 15, months one, two and three and every three months thereafter.Results:Significant improvements in total BPRS scores, BPRS positive symptoms and anergia factor were recorded and resulted in two distinct patterns of outcome. The improvements in BPRS scores translated into marked changes in health care utilisation and in sheltered employment. Of the side effects noted, dry mouth was more common in the first month after wash-out (three patients), while hypersalivation was more frequent after this period (eight patients). There was no agranulocytosis in this cohort. Two cases of eosinophilla occurred during the first month. Weight gain affected six patients.Conclusions:We found that clozapine offers particular benefits for some treatment-resistant schizophrenic patients despite the increased hematologic risk. Our study also indicates that the beneficial effects of clozapine are delayed in relation to negative symptoms as compared with positive symptoms.

Dexamethasone suppression test in chronic schizophrenia

1988 ◽  
Vol 3 (3) ◽  
pp. 189-194 ◽  
Author(s):  
S.D. Soni ◽  
A. Mallik ◽  
V. Harris ◽  
J. Shrimanker ◽  
J. McMurray
Keyword(s):  
Negative Symptoms ◽  
Rating Scale ◽  
Chronic Schizophrenia ◽  
Neuroleptic Treatment ◽  
Brief Psychiatric Rating Scale ◽  
Structural Abnormalities ◽  
Psychiatric Rating ◽  
Suppression Test ◽  
Psychiatric Rating Scale ◽  
Anxiety Depression

SummaryDexamethasone suppresson test (DST) was administered to 26 chronic schizophrenic inpatients who were on stable doses of neuroleptics for over 3 months. Clinical assessments were made on the Brief Psychiatric Rating Scale (BPRS), the Manchester Scale (KGV) and the Scale for the Assessment of Negative Symptoms (SANS). Patients’ neuroleptic treatment was then stopped for 4 weeks and the clinical assessements and the DST repeated. Thirty two percent of the patients showed DST non-suppression which was mostly stable over the 4-week period of the study and was unaffected by the neuroleptic treatment. Contrary to some reports in the literature, the clinical rating scores (including those for depression and negative symptoms), in our patients, showed no relationship with the DST status. We suggest that the DST abnormality in chronic schizophrenies may result from two quite different mechanisms: one due to stress assoeiated with transient psychopathology such as agitation, anxiety, depression or psychotic perturbation which is transient, the other resulting from structural abnormalities in the brain and which remains stable over time.

scholarly journals Clozapine Treatment in Patients with Prior Substance Abuse

2003 ◽  
Vol 48 (2) ◽  
pp. 111-114 ◽  
Author(s):  
Deanna L Kelly ◽  
Elizabeth A Gale ◽  
Robert R Conley
Keyword(s):  
Substance Abuse ◽  
Rating Scale ◽  
Therapeutic Option ◽  
Research Unit ◽  
Treatment Resistant ◽  
Clozapine Treatment ◽  
History Of ◽  
Psychiatric Rating ◽  
Psychiatric Rating Scale ◽  
One Year

Objective: This study examined outcomes following discharge on clozapine for treatment-resistant schizophrenia patients with and without diagnosed substance abuse histories. Methods: Those discharged on clozapine from a research unit between April 1991 and March 1996 were followed with respect to hospitalization status. Of the treatment-resistant patients with schizophrenia, 19 were diagnosed as individuals with substance abuse, while 26 patients had no history of abuse. Patients were openly treated with clozapine and were included in the study if they were stabilized and discharged on the medication. Results: Patients who had histories of abuse exhibited a better treatment response and a lower total Brief Psychiatric Rating Scale (BPRS) score at discharge, compared with the non–substance abuse group. One-year readmission rates were 21% and 23% in patients with and without prior substance abuse histories, respectively ( P = ns). Conclusions: Clozapine may be a therapeutic option for the dually diagnosed population and may offer benefits to patients with schizophrenia who have a history of substance abuse.

Adjunctive memantine for schizophrenia: a meta-analysis of randomized, double-blind, placebo-controlled trials

2017 ◽  
Vol 48 (1) ◽  
pp. 72-81 ◽  
Author(s):  
W. Zheng ◽  
X-H. Li ◽  
X-H. Yang ◽  
D-B. Cai ◽  
G. S. Ungvari ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Rating Scale ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Neurocognitive Performance ◽  
Double Blind ◽  
Significant Difference ◽  
Psychiatric Rating ◽  
Psychiatric Rating Scale ◽  
Mean Differences

BackgroundDysfunction of N-methyl-D-aspartate receptor (NMDAR) is involved in the pathophysiology of schizophrenia. A meta-analysis of randomized controlled trials (RCTs) was conducted to examine the efficacy and safety of memantine, a non-competitive NMDAR antagonist, in the treatment of schizophrenia.MethodsStandardized/weighted mean differences (SMDs/WMDs), risk ratio (RR), and their 95% confidence intervals (CIs) were calculated and analyzed.ResultsIncluded in the meta-analysis were eight RCTs (n = 452) of 11.5 ± 2.6 weeks duration, with 229 patients on memantine (20 mg/day) and 223 patients on placebo. Adjunctive memantine outperformed placebo in the measures of Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale negative symptoms [SMD: −0.63 (95% CI −1.10 to −0.16), p = 0.009, I2 = 77%], but not in the total, positive and general symptoms [SMD: −0.46 to −0.08 (95% CI −0.93 to 0.22), p = 0.06–0.60, I2 = 0–74%] or the Clinical Global Impression Severity Scale [WMD: 0.04 (95% CI −0.24 to 0.32), p = 0.78]. The negative symptoms remained significant after excluding one outlying RCT [SMD: −0.41 (95% CI −0.72 to −0.11), p = 0.008, I2 = 47%]. Compared with the placebo group, adjunctive memantine was associated with significant improvement in neurocognitive function using the Mini-Mental State Examination (MMSE) [WMD: 3.09, (95% CI 1.77–4.42), p < 0.00001, I2 = 22%]. There was no significant difference in the discontinuation rate [RR: 1.34 (95% CI 0.76–2.37), p = 0.31, I2 = 0%] and adverse drug reactions between the two groups.ConclusionsThis meta-analysis showed that adjunctive memantine appears to be an efficacious and safe treatment for improving negative symptoms and neurocognitive performance in schizophrenia. Higher quality RCTs with larger samples are warranted to confirm these findings.

Effects of Neuroleptic Reduction in Schizophrenic Outpatients Receiving High Doses

1994 ◽  
Vol 39 (4) ◽  
pp. 223-229 ◽  
Author(s):  
Gérard Leblanc ◽  
Hugues Cormier ◽  
Marie-Andrée Gagné ◽  
Sylvie Vaillancourt
Keyword(s):  
Negative Symptoms ◽  
Rating Scale ◽  
High Dose ◽  
Clinical Effects ◽  
Relative Paucity ◽  
Brief Psychiatric Rating Scale ◽  
Psychiatric Rating ◽  
Psychiatric Rating Scale ◽  
High Doses ◽  
Schizophrenic Outpatients

This paper presents an open study which evaluated the clinical effects of a partial and progressive reduction in neuroleptic medication in 32 outpatients suffering from schizophrenia who were receiving high doses (equivalent of ≥ 18 mg of oral haloperidol per day; EHL). After an observation period of twelve weeks, each subject's dose of neuroleptics was reduced by 50% at the rate of 10% every four weeks. Patients were receiving a mean of 62 mg per day EHL at the beginning of the study and 30 mg per day EHL at the completion of the study. After the reduction, the following was observed: 1. a significant but modest change in psychopathology: a decrease in negative symptoms and in the total score on Brief Psychiatric Rating Scale; and 2. a significant increase in tardive dyskinesia symptoms. Six subjects relapsed but five of them recovered without increasing their reduced medication. Results of this study are discussed in the context of trying to find a minimal maintenance dose in the treatment of schizophrenia. The relative paucity of change despite a large reduction in medication argues for réévaluation of dosage in patients on high or very high doses of neuroleptics. The results suggest that many patients taking high doses could be maintained on significantly lower doses of neuroleptics. With gradual reduction of medication it would seem that many patients who are receiving a high dose of neuroleptic can achieve a lower dose than their current maintenance level.

The Efficacy of Electroconvulsive Therapy in the Treatment of Schizophrenia

1987 ◽  
Vol 151 (2) ◽  
pp. 152-155 ◽  
Author(s):  
K. R. Abraham ◽  
P. Kulhara
Keyword(s):  
Electroconvulsive Therapy ◽  
Rating Scale ◽  
Double Blind Trial ◽  
Double Blind ◽  
Blind Trial ◽  
Brief Psychiatric Rating Scale ◽  
Psychiatric Rating ◽  
Psychiatric Rating Scale ◽  
To Receive

The efficacy of ECT was investigated in a double-blind trial. Twenty-two patients with schizophrenia received trifluoperazine and were randomly allocated to receive eight real or eight simulated ECTs. In the first eight weeks, the group receiving real ECTs showed significantly more improvement as measured on the Brief Psychiatric Rating Scale. However, the groups showed no significant differences from the twelfth week onwards. The superiority of real ECT was not confirmed at the end of six months.

scholarly journals Time course of improvement with antipsychotic medication in treatment-resistant schizophrenia

2011 ◽  
Vol 199 (4) ◽  
pp. 275-280 ◽  
Author(s):  
Takefumi Suzuki ◽  
Gary Remington ◽  
Tamara Arenovich ◽  
Hiroyuki Uchida ◽  
Ofer Agid ◽  
...  
Keyword(s):  
Antipsychotic Medication ◽  
Time Course ◽  
Rating Scale ◽  
Antipsychotic Treatment ◽  
Treatment Resistant ◽  
Item Score ◽  
Double Blind ◽  
The Mean ◽  
Meta Regression ◽  
Item Scores

BackgroundImprovements are greatest in the earlier weeks of antipsychotic treatment of patients with non-resistant schizophrenia.AimsTo address the early time-line for improvement with antipsychotics in treatment-resistant schizophrenia.MethodRandomised double-blind trials of antipsychotic medication in adult patients with treatment-resistant schizophrenia were investigated (last search June 2010). A series of meta-regression analyses were carried out to examine the effect of time on the average item scores in the Positive and Negative Syndrome Scale (PANSS) or Brief Psychiatric Rating Scale (BPRS) at three or more distinct time points within the first 6 weeks of treatment.ResultsStudy duration varied from 4 weeks to 1 year and the definitions of treatment resistance as well as of treatment response were not necessarily consistent across 19 identified studies, resulting in highly variable rates of response (0–76%). The mean standardised baseline item score in the PANSS or BPRS was 3.4 (s.e. = 0.06) in the five studies included in the meta-regression analysis, with the average baseline Clinical Global Impression – Severity score being 5.2 (marked illness). For the pooled population treated with a range of antipsychotics (n = 1019), significant reductions in the mean item scores occurred during the first 4 weeks; improvements observed in later weeks were smaller and non-significant. In contrast, weekly improvement with clozapine was significant throughout (n = 356).ConclusionsOur findings provide preliminary evidence that the majority of improvement with antipsychotics may occur relatively early. More consistent improvements with clozapine may be associated with a gradual titration. To further elucidate response patterns, future studies are needed to provide data over regular intervals during earlier stages of treatment.

scholarly journals Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial

2018 ◽  
Vol 49 (4) ◽  
pp. 655-663 ◽  
Author(s):  
Fernanda Palhano-Fontes ◽  
Dayanna Barreto ◽  
Heloisa Onias ◽  
Katia C. Andrade ◽  
Morgana M. Novaes ◽  
...  
Keyword(s):  
Rating Scale ◽  
Remission Rate ◽  
Controlled Trial ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Open Label ◽  
Double Blind ◽  
Therapeutic Value ◽  
Antidepressant Effects ◽  
Resistant Depression

AbstractBackgroundRecent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression.MethodsTo test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing.ResultsWe observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p= 0.04), and at D7 (p< 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen'sd= 0.84; D2: Cohen'sd= 0.84; D7: Cohen'sd= 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64%v.27%;p= 0.04). Remission rate showed a trend toward significance at D7 (36%v.7%,p= 0.054).ConclusionsTo our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered athttp://clinicaltrials.gov(NCT02914769).

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