Pharmacological management of treatment-resistant schizophrenia: alternatives to clozapine

2018 ◽  
Author(s):  
Thomas R. E. Barnes
Keyword(s):  
Antipsychotic Medication ◽  
Mood Stabilizers ◽  
High Dose ◽  
Treatment Resistant ◽  
Pharmacological Interventions ◽  
Pharmacological Management ◽  
Individual Trial ◽  
Augmentation Strategy ◽  
Risk Balance ◽  
Robust Evidence

Other than for clozapine, there are no pharmacological interventions with robust evidence of a positive benefit–risk balance for the treatment-resistant schizophrenia. For patients with treatment-resistant schizophrenia, there is usually little to be gained, in comparison to switching the antipsychotic to clozapine, from alternatives such as a further switch to a non-clozapine antipsychotic medication, the prescription of high-dose or combined antipsychotic medications, or the augmentation of continuing antipsychotic medication with other medications, such as antidepressants, mood stabilizers, or benzodiazepines. However, where these are tried, each initiation of high-dose or combined antipsychotic medication or an augmentation strategy should be treated as an individual trial and appropriately monitored and reviewed, with discontinuation in case of inefficacy or benefit that is outweighed by safety or tolerability concerns.

Augmentation Strategies for Clozapine-Resistant Patients with Schizophrenia

2020 ◽  
Vol 26 (2) ◽  
pp. 218-227
Author(s):  
Yi-Hang Chiu ◽  
Chia-Yueh Hsu ◽  
Mong-Liang Lu ◽  
Chun-Hsin Chen
Keyword(s):  
Sample Size ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Mood Stabilizers ◽  
Treatment Resistant ◽  
Double Blind ◽  
Beneficial Effects ◽  
Augmentation Strategies ◽  
Pubmed Database ◽  
Augmentation Strategy ◽  
Larger Sample

Background: Clozapine has been used in treatment-resistant patients with schizophrenia. However, only 40% of patients with treatment-resistant schizophrenia have response to clozapine. Many augmentation strategies have been proposed to treat those clozapine-resistant patients, but the results are inconclusive. In this review, we intended to review papers dealing with the augmentation strategies in the treatment of clozapineresistant patients with schizophrenia. Method: We reviewed randomized, double-blind, placebo- or sham-controlled trials (RCT) for clozapine-resistant patients with schizophrenia in Embase, PsycINFO, Cochrane, and PubMed database from January 1990 to June 2019. Results: Antipsychotics, antidepressants, mood stabilizers, brain stimulation, such as electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation, and other strategies, were used as an augmentation in clozapine-resistant patients with schizophrenia. Except for better evidence in memantine with 2 RCTs and cognitive behavior therapy in 2 studies to support its effectiveness, we found that all the other effective augmentations, including sulpiride, ziprasidone, duloxetine, mirtazapine, ECT, sodium benzoate, ginkgo biloba, and minocycline, had only one RCT with limited sample size. Conclusion: In this review, no definite effective augmentation strategy was found for clozapine-resistant patients. Some potential strategies with beneficial effects on psychopathology need further studies with a larger sample size to support their efficacy.

scholarly journals New drugs, old problems: Revisiting… Pharmacological management of treatment-resistant depression

2005 ◽  
Vol 11 (1) ◽  
pp. 19-27 ◽  
Author(s):  
Philip J. Cowen
Keyword(s):  
Antidepressant Medication ◽  
New Drugs ◽  
Care Plan ◽  
Supporting Evidence ◽  
Treatment Resistant ◽  
Pragmatic Trials ◽  
Pharmacological Management ◽  
Augmentation Strategy ◽  
Resistant Depression ◽  
Antidepressant Combination

Effective pharmacological management of depression resistant to antidepressant medication is best carried out in the context of a supportive and collaborative relationship, following a mutually agreed care plan. Simpler pharmacological approaches such as switching antidepressant classes are tried first, then augmentation is used if needed. New classes of antidepressants have made antidepressant combination a popular augmentation strategy, but lithium addition has most supporting evidence. The use of atypical antipsychotics as augmenting agents is increasing. For patients unresponsive to these strategies, monoamine oxidase inhibitors and electroconvulsive therapy remain important. Large randomised pragmatic trials are needed to help clinicians and patients make better treatment choices.

Adverse Effects and Laboratory Parameters of High-Dose Olanzapine vs. Clozapine in Treatment-Resistant Schizophrenia

2003 ◽  
Vol 15 (3) ◽  
pp. 181-186 ◽  
Author(s):  
Deanna Kelly ◽  
Robert Conley ◽  
Charles Richardson ◽  
Carol Tamminga ◽  
William Carpenter
Keyword(s):  
Adverse Effects ◽  
High Dose ◽  
Treatment Resistant ◽  
Laboratory Parameters

ADHD with Comorbid Bipolar Disorders: A Systematic Review of Neurobiological, Clinical and Pharmacological Aspects Across the Lifespan

2019 ◽  
Vol 26 (38) ◽  
pp. 6942-6969 ◽  
Author(s):  
Federico Mucci ◽  
Maria Teresa Avella ◽  
Donatella Marazziti
Keyword(s):  
Clinical Features ◽  
Adult Adhd ◽  
Neurodevelopmental Disorder ◽  
Bipolar Disorders ◽  
Mood Stabilizers ◽  
Disruptive Behaviour ◽  
Single Individual ◽  
Pharmacological Management ◽  
Long Time ◽  
The Individual

Background: Attention deficit hyperactivity (ADHD) disorder is a neurodevelopmental disorder characterized by inattention, hyperactivity, disruptive behaviour, and impulsivity. Despite considered typical of children for a long time, the persistence of ADHD symptoms in adulthood gained increasing interest during the last decades. Indeed, its diagnosis, albeit controversial, is rarely carried out even because ADHD is often comorbid with several other psychiatric diosrders, in particular with bipolar disorders (BDs), a condition that complicates the clinical picture, assessment and treatment. Aims: The aim of this paper was to systematically review the scientific literature on the neurobiological, clinical features and current pharmacological management of ADHD comorbid with BDs across the entire lifespan, with a major focus on the adulthood. Discussion: The pharmacology of ADHD-BD in adults is still empirical and influenced by the individual experience of the clinicians. Stimulants are endowed of a prompt efficacy and safety, whilst non-stimulants are useful when a substance abuse history is detected, although they require some weeks in order to be fully effective. In any case, an in-depth diagnostic and clinical evaluation of the single individual is mandatory. Conclusions: The comorbidity of ADHD with BD is still a controversial matter, as it is the notion of adult ADHD as a distinct nosological category. Indeed, some findings highlighted the presence of common neurobiological mechanisms and overlapping clinical features, although disagreement does exist. In any case, while expecting to disentangle this crucial question, a correct management of this comorbidity is essential, which requires the co-administration of mood stabilizers. Further controlled clinical studies in large samples of adult ADHD-BD patients appear extremely urgent in order to better define possible therapeutic guidelines, as well as alternative approaches for this potentially invalidating condition.

scholarly journals Treatment-resistant schizophrenia characterised by dopamine supersensitivity psychosis and efficacy of asenapine

2021 ◽  
Vol 14 (4) ◽  
pp. e242495
Author(s):  
Nagara Takao ◽  
Toshiya Murai ◽  
Hironobu Fujiwara
Keyword(s):  
Animal Studies ◽  
Significant Proportion ◽  
Antipsychotic Treatment ◽  
High Dose ◽  
Receptor Density ◽  
Treatment Resistant ◽  
Psychomotor Activity ◽  
Receptor Blockers ◽  
Dopamine Supersensitivity

Dopamine supersensitivity psychosis (DSP) frequently arises with long-term antipsychotic treatment and accounts for a significant proportion of treatment-resistant schizophrenia. The mechanism underlying DSP is thought to be a compensatory increase in dopamine receptor density in the striatum caused by long-term antipsychotic treatment. Previous animal studies have reported that antipsychotics increase serotonin 5-HT2A receptor density in the striatum and that 5-HT2A receptor blockers suppress dopamine-sensitive psychomotor activity, which may be linked to the pathophysiology of DSP. In this paper, we describe a patient who was hospitalised with treatment-resistant schizophrenia. Following treatment with high-dose antipsychotic polypharmacy for 10 weeks, the patient experienced worsening of psychotic and extrapyramidal symptoms. The patient was then started on second-generation antipsychotic asenapine while other antipsychotics were tapered off, resulting in improvement of these symptoms. Retrospectively, we presumed that the high-dose antipsychotic polypharmacy caused DSP, which was effectively treated by the potent 5-HT2A receptor antagonism of asenapine.

A pilot double-blind comparison of d-serine and high-dose olanzapine in treatment-resistant patients with schizophrenia

2013 ◽  
Vol 150 (2-3) ◽  
pp. 604-605 ◽  
Author(s):  
Marina Ermilov ◽  
Evgenia Gelfin ◽  
Raz Levin ◽  
Pesach Lichtenberg ◽  
Kenji Hashimoto ◽  
...  
Keyword(s):  
High Dose ◽  
Treatment Resistant ◽  
Double Blind ◽  
Blind Comparison

scholarly journals Use of psychotropic medication in seven English psychiatric intensive care units

2010 ◽  
Vol 34 (4) ◽  
pp. 130-135 ◽  
Author(s):  
Steve Brown ◽  
Navjyoat Chhina ◽  
Stephen Dye
Keyword(s):  
Intensive Care ◽  
Intensive Care Units ◽  
Antipsychotic Drug ◽  
Antipsychotic Medication ◽  
Psychotropic Medication ◽  
Intramuscular Injection ◽  
Case Note ◽  
Clinical Implications ◽  
High Dose ◽  
Prescribing Practices

Aims and methodTo describe the psychotropic medication given to 332 patients admitted consecutively to seven English psychiatric intensive care units (PICUs) by prospective, multicentre case-note analysis.ResultsOverall, 104 (32%) patients received rapid tranquillisation or zuclopenthixol acetate by intramuscular injection; 72 (23%) received more than one regular antipsychotic drug simultaneously. It was reported that 20 patients received high-dose antipsychotic medication, which was probably an underestimate. The use of these interventions varied significantly between different units.Clinical implicationsPotentially risky treatments such as forcible intramuscular medication are a standard part of PICU activity. Further work is needed to clarify the reasons behind the differences in prescribing practices between different PICUs.

Augmentation strategies in the treatment of major depressive disorder

2016 ◽  
Vol 33 (S1) ◽  
pp. S407-S407
Author(s):  
S. Bise ◽  
B. Kurtovic ◽  
D. Begic ◽  
O. Cemalovic
Keyword(s):  
Major Depressive Disorder ◽  
Combination Therapy ◽  
Depressive Disorder ◽  
Mood Stabilizers ◽  
Augmentation Therapy ◽  
Major Depressive ◽  
Augmentation Strategies ◽  
Significant Difference ◽  
Augmentation Strategy ◽  
Competing Interest

Augmentation strategies for the treatment of Major depressive disorder (MDD) are needed when patients with MDD have a partial, or not responded to antidepressant monotherapy. The focus of augmentation therapy has been combining an antidepressant (AD) medication with another AD. Atypical antipsychotics (AAP) are becoming commonly used to augment antidepressants. Beyond AD and AAP, alternative augmentation strategies include mood stabilizers (MS).AimTo analyze the characteristics of therapy in patients with diagnosis of MDD and to investigate the frequency of augmentation therapy.MethodStudy included 28 patients hospitalized during one year with MDD diagnosis. Statistical analysis was performed with x2 and t-test.ResultAmong patients with MDD there were 18 (64.28%) women with an average age 57.5 and 10 (35.71%) men with an average age 53.5. Of the 28 patients with MDD, 25 (89.28%) were treated with a combination therapy, and monotherapy in the remaining 3 patients (10.71%). Of 25 patients with augmentation strategy treatment, 22 (88%) used two medications and the remaining 3 (12%) tree psychotropic medications (AAP, AD, MS). The most frequent combinations were a combination of AD and AAP (17 patients, 68%). Beyond that frequent combination were AD and MS (6 patients, 24%). Two patients used combination two AAP, and one patient with two AD and one patients used AAP and MS.ConclusionAugmentation strategy is often used in patients with MDD. There is no significant difference in the use combination therapy based on gender and age.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Reducing the use of high dose antipsychotic medication in acute adult inpatient psychiatric units

BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S341-S341
Author(s):  
Shay-Anne Pantall ◽  
Sarah Warwicker ◽  
Lisa Brownell
Keyword(s):  
Antipsychotic Medication ◽  
Psychiatric Inpatient ◽  
Electronic Prescribing ◽  
Antipsychotic Treatment ◽  
High Dose ◽  
Junior Doctors ◽  
List Type ◽  
Increased Risk ◽  
Adult Inpatient ◽  
Inpatient Units

AimsTo evaluate the use of antipsychotics, and high dose antipsychotic treatment (HDAT) in psychiatric inpatient unitsBackgroundThe Royal College of Psychiatrists published a consensus statement on high dose antipsychotic medication in October 1993. Such treatment carries an increased risk of adverse effects including towards ventricular tachycardia and sudden death.MethodA retrospective case note review of all male patients on acute adult inpatient units in a psychiatric hospital in South Birmingham on a date in June 2018 (n = 45) including review of electronic patient records and prescriptions. This was compared with the results of an earlier study, with identical methods, undertaken in June 2015.Result•In both 2015 and 2018, only a minority of patients (20% and 11% respectively) were informal.•In both 2015 and 2018, the majority of inpatients had a diagnosis of schizophrenia (54% and 67%)•In both 2015 and 2018, 93% inpatients were prescribed antipsychotic medication.•In 2015, 56% patients were prescribed HDAT. This reduced in 2018 to 16%.•This reduction in use of HDAT was almost entirely due to a reduction in the prescription of PRN antipsychotic medication.•In terms of regularly prescribed antipsychotic medication, in both years, the most commonly prescribed drug was flupentixol, with a range of other second generation oral and long acting medications being prescribed, usually at doses within BNF limits.Between the two years, there was a substantial change in the prescribing of PRN antipsychotics. In 2015, 59% individuals were prescribed at least one PRN antipsychotic (27% were prescribed two). In 2018, this reduced to 40% prescribed at least one, and only 2% being prescribed 2 PRN antipsychotics. In both years, oral quetiapine was a common choice (39% patients in 2015 prescribed oral quetiapine, and 34% in 2018). In 2015, 39% patients were prescribed oral or intramuscular aripiprazole, while this reduced to 7% in 2018.ConclusionThe vast majority of psychiatric inpatients were being prescribed antipsychotic medication. Prescription of high dose antipsychotic medication was common in 2015, and this was largely attributable to high levels of prescribing of PRN antipsychotics. Following an educational programme for junior doctors and ward nurses, and the introduction of electronic prescribing, we achieved a significant change in practice, particularly in the prescribing of PRN antipsychotics, which has reduced our patients’ risk of receiving high dose antipsychotic medication.

scholarly journals High-dose olanzapine in treatment resistant schizophrenia. A case report and literature review

BJPsych Open ◽  
2021 ◽  
Vol 7 (S1) ◽  
pp. S115-S115
Author(s):  
Ciara Clarke ◽  
Clodagh Rushe ◽  
Fintan Byrne
Keyword(s):  
Case Report ◽  
Literature Review ◽  
The Body ◽  
Psychotic Symptoms ◽  
High Dose ◽  
Extensive Literature ◽  
Treatment Resistant ◽  
Persecutory Delusions ◽  
Full Resolution ◽  
One Year

ObjectiveWe report a case of a 58-year-old gentleman who was hospitalised intermittently for one year due to treatment resistant schizophrenia. Prior to hospitalisation he had been prescribed standard antipsychotics for decades without full resolution of positive psychotic symptoms. During his final admission lasting six months he was guarded, suspicious, irritable, constantly paced the corridor and displayed thought block and paranoid persecutory delusions. He would not enter the assessment room or allow any blood or ECG monitoring, however, he was compliant with oral medication. He was successfully treated with high dose olanzapine (40mg/day) and was discharged to the community. The aim of this study is to bring awareness and add to the body of evidence for the use of high-dose olanzapine in patients with treatment resistant schizophrenia in whom a trial of clozapine is not possible.Case reportThe patient gave written consent for this case report to be written and presented. An extensive literature review was performed and key papers were identified. Discussion focuses on the key areas in the literature.DiscussionThis case demonstrates that high-dose olanzapine can be used effectively as an alternative to clozapine in treatment resistant schizophrenia.ConclusionThis case highlights the need for further evaluation of high-dose olanzapine as an alternative to clozapine in patients with treatment-resistant schizophrenia.

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