Psychopharmacological Treatment for Psychological Distress
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Icahn School of Medicine at Mount Sinai
Must not be taking: Clonazepam, Olanzapine, Opiate agonists, others
Disqualifiers: Intellectual disability, Opiate use, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This is an inpatient four-arm randomized control trial comparing single drug clonazepam (S arm), a two-drug combination clonazepam/olanzapine (D arm), and a three-drug combination clonazepam/olanzapine/buprenorphine (T arm) with treatment as usual (TAU arm) in the treatment of emotional distress, specifically the Suicide Crisis Syndrome (SCS). All participants in experimental arms receive 2-day pulse treatments targeting four out of five of the acute emotional distress symptoms. The primary outcome measure is SCS at discharge and one-month follow-up. The secondary outcome measures include questions about suicidal behaviors associated with emotional distress at a one-month follow-up.
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications, but you cannot participate if you are currently being treated with clonazepam or olanzapine.
What data supports the effectiveness of the drug Olanzapine for psychological distress?
Research suggests that Olanzapine, which is similar to another drug called Clozapine, has been used to treat severe mental health conditions like schizophrenia, but its effectiveness can vary. In some studies, it did not show significant improvement for patients with treatment-resistant psychosis, indicating that its benefits might be limited in certain cases.
12345Is olanzapine generally safe for humans?
Olanzapine is generally considered safe for humans, as studies have shown it to be well-tolerated with no significant changes in vital signs or laboratory measures. However, it may cause weight gain and metabolic issues, and some patients may experience increased agitation when starting the treatment.
16789How does the drug Buprenorphine differ from other treatments for psychological distress?
Buprenorphine is unique because it is typically used to treat opioid addiction by reducing withdrawal symptoms and cravings, which is different from traditional treatments for psychological distress that often focus on directly altering mood or anxiety levels.
12101112Eligibility Criteria
This trial is for individuals recently hospitalized due to emotional distress or a suicide attempt, who can understand the study and agree to stay in the hospital for at least 4 days. It's not for those with past bad reactions to clonazepam, olanzapine, or buprenorphine, history of substance abuse disorders within two years, current opiate addiction treatment, significant medical conditions affecting consent ability, involuntary psychiatric treatment, or suspected malingering.Inclusion Criteria
You are able and willing to provide contact information that can be checked.
The patient has been admitted to a hospital and has been diagnosed with SCS using SCS-C.
You can understand and agree to the information in the consent form.
+4 more
Exclusion Criteria
I am currently taking clonazepam or olanzapine.
I do not have any serious health or brain conditions that could affect my participation.
Undomiciled
+6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
1-2 weeks
Treatment
Participants receive 2-day pulse treatments with clonazepam, clonazepam/olanzapine, or clonazepam/olanzapine/buprenorphine targeting acute emotional distress symptoms
2 days
Inpatient Monitoring
Participants are monitored for the primary outcome measure, Suicide Crisis Syndrome, during their inpatient stay
up to discharge
Follow-up
Participants are monitored for safety and effectiveness after treatment, including assessment of Suicide Crisis Syndrome and suicidal behaviors
1 month
Participant Groups
The trial compares three medication strategies (clonazepam alone; clonazepam with olanzapine; and all three drugs together) against standard care over a short period. The goal is to see which method best reduces acute emotional distress symptoms associated with Suicide Crisis Syndrome immediately after treatment and one month later.
4Treatment groups
Experimental Treatment
Active Control
Group I: T arm: Three-drug combination clonazepam/olanzapine/buprenorphineExperimental Treatment3 Interventions
Three-drug combination clonazepam/olanzapine/buprenorphine: 1 mg a day (0.5 mg twice a day) of Clonazepam plus 2.5 mg a day of Olanzapine plus 2mg a day of Buprenorphine with Treatment As Usual (TAU)
Group II: S arm: Single drug clonazepamExperimental Treatment1 Intervention
Single drug clonazepam: 1 mg a day (0.5 mg twice a day) with Treatment As Usual (TAU)
Group III: D arm: Two-drug combination clonazepam/olanzapineExperimental Treatment2 Interventions
Two-drug combination clonazepam/olanzapine: 1 mg a day (0.5 mg twice a day) of Clonazepam plus 2.5 mg a day of Olanzapine with Treatment As Usual (TAU)
Group IV: Control GroupActive Control1 Intervention
Participants that will not receive an intervention.
Buprenorphine is already approved in United States, European Union for the following indications:
馃嚭馃嚫 Approved in United States as Buprenorphine for:
- Moderate to severe opioid addiction (dependence)
馃嚜馃嚭 Approved in European Union as Buprenorphine for:
- Opioid dependence
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Icahn School of Medicine at Mount SinaiNew York, NY
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Who Is Running the Clinical Trial?
Icahn School of Medicine at Mount SinaiLead Sponsor
References
An open trial of olanzapine in patients with treatment-refractory psychoses. [2019]Olanzapine's structural similarities to clozapine and the results of premarketing clinical trials suggested potential usefulness in treating patients with treatment-refractory psychoses. Sixteen inpatients from the state hospital with severe, refractory schizophrenic or schizoaffective psychoses received olanzapine in a prospective, 12-week, open-label trial. The olanzapine dose was 10 mg/day for at least the first 6 weeks and never exceeded 20 mg/day. Mood stabilizers and other antipsychotic agents were discontinued before olanzapine was started. Patients frequently became more agitated within the first several weeks of initiating treatment, requiring the increased use of benzodiazepines and often leading to the discontinuation of olanzapine. Two patients improved significantly. Overall, significant clinical improvement was noted only for motor side effects. This study concluded that olanzapine was not effective in this heterogeneous group with chronic, severe, treatment-resistant psychosis when used in this manner. Further research is needed to explain the tendency toward agitation upon transition to olanzapine, which is reminiscent of reported risperidone complications. Clinicians should be alert for this complication and should minimize concomitant medication changes that might add to the risk of emergent agitation.
Augmentation of clozapine with a second antipsychotic--a meta-analysis of randomized, placebo-controlled studies. [2013]Inadequate response to clozapine treatment is frequently encountered in practice and augmentation strategies have been developed in an attempt to improve response. Aims of the study were to evaluate the therapeutic effect of adding an antipsychotic drug to clozapine treatment.
Antipsychotic Polypharmacy in Clozapine Resistant Schizophrenia: A Randomized Controlled Trial of Tapering Antipsychotic Co-treatment. [2020]There is a considerable disparity between clinical practice and recommendations based on meta-analyses of antipsychotic polypharmacy in clozapine resistant schizophrenia. For this reason, we investigated the clinical response to reducing the use olanzapine that had been previously added on clozapine treatment among seriously ill hospitalized patients. In a randomized controlled trial with crossover design, we studied volunteer patients (N=15) who had olanzapine added on to clozapine in a state mental hospital. Clozapine monotherapy was just as effective as clozapine-olanzapine therapy, according to results from Clinical Global Impression Scale and Global Assessment of Functioning as primary outcome measures. Polypharmacy is widely used in treating schizophrenia, and usually, add-on medications are started because of worsening of the clinical state. A major confounding feature of these add-ons is whether observed improvements are caused by the medication or explained by the natural fluctuating course of the disorder. The present study, in spite of its small size, indicates the necessity of reconsidering the value of polypharmacy in treating schizophrenia.
Managing treatment-resistant schizophrenia: evidence from randomized clinical trials. [2019]Clozapine was the first antipsychotic medication to be approved for the indication of treatment-refractory schizophrenia. This followed rigorous testing in patients who retrospectively and prospectively failed treatment trials of relatively high doses of conventional antipsychotics. In the past decade, other atypical antipsychotics have been approved, but they have not been designated specifically for patients with a history of prior poor treatment response. Better tolerated than clozapine, these new agents have been used with varying success in patients who would have otherwise received clozapine. Up until very recently there has not been a head-to-head controlled clinical trial comparing the two most commonly used atypical antipsychotics, risperidone and olanzapine, with clozapine in patients considered to have a suboptimal response to typical antipsychotics. This review summarizes the current advances made in the pharmacological management of these patients by examining recently published randomized controlled clinical trials that have measured psychopathology and cognition.
[Augmenting atypical antipsychotic medications with clozapin]. [2018]Typical antipsychotic medications have considerably improved clinical outcome of patients suffering from schizophrenic psychoses, but up to 40% of the cases show treatment resistant symptoms. Even therapy with atypical antipsychotic drugs such as risperidone, quetiapine, olanzapine, sulpiride, amisulpride, and ziprasidone often fails to reach complete remission due to resistant, positive or negative symptoms or dose-limiting side effects. As this also holds true in the case of monotherapy with clozapine, a substance known to be effective against treatment-resistant schizophrenia, increasing numbers of patients receive atypical antipsychotic drugs in addition to clozapine. This review systematically evaluates case reports and clinical investigations on the use of clozapine combined with risperidone, olanzapine, quetiapine, sulpiride, amisulpride, or ziprasidone. Details on indication, methodology, and effects of the investigations are summarized. Only one double blind, placebo-controlled trial on the combination with sulpiride exists within a number of altogether 31 publications about 1182 treatments. Favorable effects on positive and/or negative symptoms or improvements of clozapine-induced side effects were described for every combination approach. In some cases pharmacokinetic interactions or serious unfavorable effects occurred. In conclusion it might be accepted that most of the combination therapies follow a neurobiological rational. There a major differences in the level of evidence that they are safe, tolerable and effective. We discuss criteria for the indication for augmenting clozapine therapy and the differential indication for existing alternatives. Additional randomized prospective trials are needed in order to evaluate these strategies systematically.
Olanzapine versus clozapine in treatment-resistant or treatment-intolerant schizophrenia. [2018]Clozapine has been the gold standard for treatment of patients with refractory schizophrenia but is associated with serious safety liabilities. This has prompted the search for therapeutic alternatives for treatment-resistant schizophrenia. The objective of this study was to compare the efficacy and safety of olanzapine versus clozapine in schizophrenic patients who failed to respond adequately to antipsychotic medication or who experienced intolerable adverse effects associated with the medication. This 18-week, randomized, double-blind, parallel study compared treatment with either olanzapine (5-25 mg/day, n=75) or clozapine (100-500 mg/day, n=72) in patients with schizophrenia who were nonresponsive to, or intolerant of, standard acceptable antipsychotic therapy. At the 18-week endpoint, no statistically significant differences were found between olanzapine and clozapine in any efficacy measure used: Positive and Negative Syndrome Scale (PANSS) total, positive, negative, or general psychopathology or Clinical Global Impression severity (CGI-S). Response rates based on the criteria of Kane et al. [Arch. Gen. Psychiatry 45 (1988) 789] were also not significantly different between olanzapine-treated (57.9%) and clozapine-treated patients (60.8%). There were no significant differences in measurements of extrapyramidal symptoms or electrocardiography, and no clinically and statistically significant changes were seen in vital signs or laboratory measures in either group. Both treatments were well tolerated. Olanzapine demonstrated similar efficacy to clozapine in patients who had failed previous treatment because of lack of efficacy (treatment resistance) or intolerable side effects (treatment intolerance). Olanzapine therefore presents a safe alternative in the treatment of refractory schizophrenia.
Olanzapine - relapse prevention following mania. [2018]This review describes the pharmacological characteristics of olanzapine (ZYPREXA), outlines the European licensed indications and examines four peer reviewed, randomized, controlled, double blind clinical trials investigating the efficacy of olanzapine as maintenance therapy in patients with bipolar I disorder. These studies range in duration from 47 to 78 weeks and support the view that olanzapine is an effective and well-tolerated pharmacological therapy for relapse prevention in bipolar disorder. Evidence is presented that olanzapine is effective in preventing relapse following an index manic or a mixed episode with or without psychotic features and in patients with a history of rapid cycling. The safety and tolerability of the medicine is also examined, focusing on weight gain and metabolic issues.
Anxious-depressive symptoms in schizophrenia: a new treatment target for pharmacotherapy? [2019]Schizophrenia patients frequently manifest concurrent anxiety and depressive symptoms. Such features exhibit prognostic relevance (i.e. patient morbidity and mortality). Despite this, they remain relatively unstudied and are not universally viewed as therapeutic targets. Conventional neuroleptic agents may not improve these symptoms and may actually worsen them. However, with the introduction of novel pharmacological agents for the treatment of schizophrenia, there is reason to believe that a wider spectrum of symptomatology may be treatment responsive. In this post hoc analysis of the Brief Psychiatric Rating Scale anxiety-depression cluster, olanzapine therapy was associated with a significantly greater baseline-to-end-point improvement in the cluster compared with haloperidol therapy among 1996 randomized, double-blind subjects. Moreover, the olanzapine treatment-effect advantage included both direct (mood symptoms) and indirect (positive, negative, and extrapyramidal symptoms) elements. This study concluded that the novel pharmacology of olanzapine delivered greater therapeutic activity in anxious and depressive symptoms accompanying schizophrenia than did the conventional dopamine D2 antagonist haloperidol.
Update on the clinical efficacy and side effects of clozapine. [2022]Clozapine (CLOZ) is an atypical antipsychotic drug being used with increasing frequency throughout the world and has recently been commercially marketed in the United States. Its unique properties make it a promising but challenging drug to use in the treatment of schizophrenia. In order to use CLOZ most effectively and efficiently, clinicians must be aware of its potential benefits and risks. This report is a review and critical evaluation of current knowledge regarding the clinical efficacy and side effects of CLOZ. Although CLOZ has proven to be effective in some treatment-refractory schizophrenic patients and to produce relatively few extrapyramidal side effects compared to classical neuroleptic drugs, several issues require further investigation including what defines neuroleptic intolerance, the optimal dose range, and the appropriate duration of a CLOZ treatment trial. Similarly, studies are needed to determine what role CLOZ should have in the treatment of patients with predominantly negative symptoms and those patients who are only partially responsive to standard neuroleptics. In addition, important questions remain as to what other conditions might be indications for CLOZ, for example, schizoaffective disorder, affective psychoses, and idiopathic Parkinson's disease.
[Psychopharmacological treatment of treatment-resistant schizophrenia]. [2013]The research criteria of treatment-resistance in schizophrenia are reviewed and discussed, and the following definition for the use in the clinic is proposed: At least two periods of treatment with conventional antipsychotics from two different chemical classes at adequate doses for a period of at least four weeks, each without significant symptomatic relief. In addition, patients have to meet the criteria of clinical significant psychopathology, reduced psychosocial function or reduced quality of life. The article also reviews efficacy studies and the recommendations for the psychopharmacological treatment of therapy-resistant schizophrenia. Placebo-controlled and open trials have shown clozapine to be clearly effective in 30-60% of patients resistant to conventional antipsychotic treatment. Up to one half of the patients may respond between three months and a year of treatment. Clozapine has been found to reduce positive and negative symptoms as well as enhancing both cognitive and psychosocial function in schizophrenics. The first drug of choice today, after treatment-resistance has been established is a trial of clozapine for at least six months. The optimal dose range of clozapine appears to be 300-600 mg/day for most patients. Some schizophrenics cannot be treated with clozapine because of contraindications or do not respond sufficiently. In these patients conventional antipsychotics have to be prescribed and augmentated with benzodiazepines, antidepressants, mood-stabilizers, or electroconvulsive treatment.
The 2009 schizophrenia PORT psychopharmacological treatment recommendations and summary statements. [2022]In light of the large number of studies published since the 2004 update of Schizophrenia Patient Outcomes Research Team psychopharmacological treatment recommendations, we conducted an extensive literature review to determine whether the current psychopharmacological treatment recommendations required revision and whether there was sufficient evidence to warrant new treatment recommendations for prespecified outcomes of interest. We reviewed over 400 articles, which resulted in 16 treatment recommendations: the revision of 11 previous treatment recommendations and 5 new treatment recommendations. Three previous treatment recommendations were eliminated. There were 13 interventions and/or outcomes for which there was insufficient evidence for a treatment recommendation, and a statement was written to summarize the current level of evidence and identify important gaps in our knowledge that need to be addressed. In general, there was considerable consensus among the Psychopharmacology Evidence Review Group and the expert consultants. Two major areas of contention concerned whether there was sufficient evidence to recommend specific dosage ranges for the acute and maintenance treatment of first-episode and multi-episode schizophrenia and to endorse the practice of switching antipsychotics for the treatment of antipsychotic-related weight gain. Finally, there continue to be major gaps in our knowledge, including limited information on (1) the use of adjunctive pharmacological agents for the treatment of persistent positive symptoms or other symptom domains of psychopathology, including anxiety, cognitive impairments, depressive symptoms, and persistent negative symptoms and (2) the treatment of co-occurring substance or medical disorders that occur frequently in individuals with schizophrenia.
Prescribing patterns and the use of therapeutic drug monitoring of psychotropic medication in a psychiatric high-security unit. [2015]The aim of this study was to investigate the use of psychotropic medication and therapeutic drug monitoring in a high-security psychiatric unit and to compare the doses and serum concentrations both with the recommended intervals and with the doses and serum concentrations in a control group. One hundred thirty-two patients were admitted in the period from January 2000 to December 2005. All available samples were used when comparing serum concentrations and doses with the recommended ranges. For the comparison of doses and serum concentration-to-dose (C:D) ratios with the control group only 1 sample from each patient was used. A total of 459 analyses of 27 different drugs in samples from 8 women and 73 men were included. The median number of therapeutic drug monitoring analyses per patient was 4 (range 1-29). Thirty-seven of the 81 patients (46%) used 2 or more antipsychotics at the same time. Clozapine, lamotrigine, olanzapine, quetiapine, ziprasidone, and zuclopenthixol were often given in doses above the recommended. The serum levels were frequently above those recommended for clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and zuclopenthixol. The serum levels were significantly higher in the study group than in the control group for clozapine, lamotrigine, quetiapine, and zuclopenthixol. The given dose was significantly higher in the study group than in the control group for clozapine, lamotrigine and zuclopenthixol. The C:D ratio was significantly lower in the study group than in the control group for olanzapine but higher for quetiapine. The non-evidence based practice of high-dose polypharmacy with several antipsychotics is widely used in this unit. The use of higher doses in the study group than in the control group was not due to differences in metabolism or adherence to treatment between the 2 groups. The frequent use of therapeutic drug monitoring did not seem to have a great impact on the prescribed doses.