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.

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 116 Retrospective Analysis of Clozapine Augmentation in Treatment-Resistant Schizophrenia in an Outpatient Setting

CNS Spectrums ◽  
2018 ◽  
Vol 23 (1) ◽  
pp. 73-74
Author(s):  
Charles Odom ◽  
Frozan Walyzada ◽  
Pankaj Manocha ◽  
Monika Gashi ◽  
Ashaki Martin ◽  
...  
Keyword(s):  
Retrospective Analysis ◽  
Treatment Options ◽  
D2 Receptor ◽  
Treatment Strategies ◽  
Outpatient Setting ◽  
Mood Stabilizers ◽  
Adjunctive Treatment ◽  
Supporting Evidence ◽  
Treatment Resistant ◽  
Augmentation Strategies

AbstractStudy ObjectivesThis retrospective analysis hopes to add to the literature about Treatment Resistant Schizophrenia (TRS), augmentation strategies with antipsychotics used in our patient population with the hopes of clarifying what possibilities should be further studied. In addition, we aim to emphasize the need for focusing on individualized treatment and multidisciplinary efforts to ensure compliance and appropriate disposition options.MethodWe reviewed retrospectively 3025 charts of patients between January 2017 to March 2017 in our outpatient department establishing which antipsychotic clozapineaugmentation strategies were being used. We also did a literature review to establish what augmentation strategies are recommended. These patients will then be compared to a random sample of patients in the clinic who were not prescribed clozapine and compared for readmission rate, side effect profile, length of stay while admitted, frequency of clinic attendance and compliance with outpatient appointments.ResultsOut of 3025 patients 35 were prescribed Clozapine as monotherapy and 5 patients had clozapine plus psychopharmacological augmentation. Ages ranged from 21-86. Out of the 39 patients, there were 13 male and 26 female. The predominant diagnosis was mood disorder or MDD with psychotic features followed by schizophrenia. The augmentation antipsychotics used were aripiprazole and risperidone. In the literature, the most frequent augmentation strategy for TRS is adding another antipsychotic with more D2 receptor blockade. Other strategies involve identifying and treating the symptoms not controlled by clozapine.ConclusionsCurrently augmentation of Clozapine in TRS is highly individualized due to lack of supporting evidence to state the contrary. When working with treatmentresistant patients who are not responding to clozapine alone, it is imperative to thoroughly review and consider all treatment options and augmentation strategies. More studies should be done in controlled settings to better evaluate possibilities as well as more evaluations to be done on other ways of augmentation of clozapine. Literature has stated between 20-60% of patients are defined as TRS. Clozapine is considered as one of the most effective treatment available at present time for TRS. Recent literature suggests despite its superior efficacy, as many as 70% of those suffering from TRS on clozapine continue to suffer from positive, negative or cognitive symptoms. The literature has abundant adjunctive treatment strategies such as the addition of antipsychotics, mood stabilizers, antidepressants, or even with the use of electroconvulsive therapy. We emphasize the importance of correctly identifying TRS patients who may benefit from the initiation of clozapine, what would be beneficial for them if they do not respond, how to tailor their treatment to target symptoms not being ameliorated, and recommend treatment in these complex cases be multidisciplinary.Funding AcknowledgementsNo funding.

scholarly journals Equivalent beneficial effects of unilateral and bilateral prefrontal cortex transcranial magnetic stimulation in a large randomized trial in treatment-resistant major depression

2013 ◽  
Vol 16 (9) ◽  
pp. 1975-1984 ◽  
Author(s):  
Paul B. Fitzgerald ◽  
Kate E. Hoy ◽  
Ajeet Singh ◽  
Ranil Gunewardene ◽  
Christopher Slack ◽  
...  
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Clinical Response ◽  
Magnetic Stimulation ◽  
Rating Scale ◽  
Remission Rate ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Controlled Trial ◽  
Treatment Resistant ◽  
Previous Response ◽  
Beneficial Effects

Abstract Repetitive transcranial magnetic stimulation treatment (rTMS) is an effective treatment for depression but the optimal methods of administration have yet to be determined. Recent studies have produced conflicting results as to whether unilateral rTMS is more or less effective than sequentially applied bilateral rTMS. To address this we conducted a trial comparing sequential bilateral rTMS to right-sided unilateral rTMS using a priming protocol. Patients with treatment-resistant depression (n = 179) were enrolled in a two-arm randomized controlled trial across a 4-wk time period. The primary outcome assessment was the Hamilton Depression Rating Scale. Overall, there was a substantial response rate of >50% (and a 40% remission rate); however, there were no significant differences in clinical response between the two treatment groups. rTMS was well tolerated with a very low discontinuation rate. There was no relationship between response in the current trial and previous response, or non-response, to electroconvulsive therapy. We found no significant differences in clinical response between sequential bilateral rTMS and right-sided unilateral rTMS applied with a priming protocol. The results of this study do not support superior efficacy of bilateral rTMS and instead suggest that other approaches should be explored to increase treatment efficacy.

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.

scholarly journals Early augmentation by using neuromodulation in psychiatric disorder: a kaleidoscopic view

CNS Spectrums ◽  
2021 ◽  
pp. 1-3
Author(s):  
Sujita Kumar Kar ◽  
Vikas Menon
Keyword(s):  
Clinical Practice ◽  
Psychiatric Disorder ◽  
Psychiatric Disorders ◽  
Psychological Treatment ◽  
Treatment Resistant ◽  
Traditional Treatment ◽  
Early Symptom ◽  
Early Return ◽  
Augmentation Strategies ◽  
Augmentation Strategy

Abstract Early augmentation is a relatively newer concept in the management of psychiatric disorders. In managing psychiatric disorders, augmentation strategies are commonly used after failed attempts of optimization of a dose of the medications and then switching to another medication. Neuromodulation methods are recommended by traditional treatment recommendations as augmenting strategies (mostly) in managing treatment-resistant/refractory cases of psychiatric disorders. Late in the process of therapy, several of these techniques are applied to the patient. However, using different neuromodulation techniques, early augmentation of the ongoing pharmacological or psychological treatment may be achieved, resulting in early symptom reduction or remission and early return to work by resuming functionality. The length of the symptomatic cycle may be shortened by early augmentation. There are several potential challenges to adopting an early augmentation strategy in clinical practice. This article discusses the concept and evidence of early augmentation strategy in managing psychiatric disorder by using neuromodulation technique and potential challenges before it.

scholarly journals Therapeutic Application of rTMS in Atypical Parkinsonian Disorders

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Chrysi Petsani ◽  
Athina-Maria Aloizou ◽  
Vasileios Siokas ◽  
Lambros Messinis ◽  
Eleni Peristeri ◽  
...  
Keyword(s):  
Repetitive Transcranial Magnetic Stimulation ◽  
Alternative Therapy ◽  
Lewy Bodies ◽  
Corticobasal Degeneration ◽  
Double Blind ◽  
Beneficial Effects ◽  
Disease Modifying Therapies ◽  
Parkinsonian Disorders ◽  
Preliminary Phase ◽  
Atypical Parkinsonian Disorders

The terms atypical parkinsonian disorders (APDs) and Parkinson plus syndromes are mainly used to describe the four major entities of sporadic neuronal multisystem degeneration: progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), multiple system atrophy (MSA), and dementia with Lewy bodies (LBD). APDs are characterized by a variety of symptoms and a lack of disease modifying therapies; their treatment thus remains mainly symptomatic. Brain stimulation via repetitive transcranial magnetic stimulation (rTMS) is a safe and noninvasive intervention using a magnetic coil, and it is considered an alternative therapy in various neuropsychiatric pathologies. In this paper, we review the available studies that investigate the efficacy of rTMS in the treatment of these APDs and Parkinson plus syndromes. Τhe majority of the studies have shown beneficial effects on motor and nonmotor symptoms, but research is still at a preliminary phase, with large, double-blind studies lacking in the literature.

The priming effect of repetitive transcranial magnetic stimulation on clinical response to electroconvulsive therapy in treatment-resistant depression: a randomized, double-blind, sham-controlled study

2021 ◽  
pp. 1-12
Author(s):  
Maud Rothärmel ◽  
Pierre Quesada ◽  
Thomas Husson ◽  
Ghina Harika-Germaneau ◽  
Clément Nathou ◽  
...  
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Clinical Response ◽  
Electroconvulsive Therapy ◽  
Magnetic Stimulation ◽  
Priming Effect ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Double Blind ◽  
Resistant Depression

Abstract Background Electroconvulsive therapy (ECT) is one of the most effective treatments for treatment-resistant depression (TRD). However, due to response delay and cognitive impairment, ECT remains an imperfect treatment. Compared to ECT, repetitive transcranial magnetic stimulation (rTMS) is less effective at treating severe depression, but has the advantage of being quick, easy to use, and producing almost no side effects. In this study, our objective was to assess the priming effect of rTMS sessions before ECT on clinical response in patients with TRD. Methods In this multicenter, randomized, double-blind, sham-controlled trial, 56 patients with TRD were assigned to active or sham rTMS before ECT treatment. Five sessions of active/sham neuronavigated rTMS were administered over the left dorsolateral prefrontal cortex (20 Hz, 90% resting motor threshold, 20 2 s trains with 60-s intervals, 800 pulses/session) before ECT (which was active for all patients) started. Any relative improvements were then compared between both groups after five ECT sessions, in order to assess the early response to treatment. Results After ECT, the active rTMS group exhibited a significantly greater relative improvement than the sham group [43.4% (28.6%) v. 25.4% (17.2%)]. The responder rate in the active group was at least three times higher. Cognitive complaints, which were assessed using the Cognitive Failures Questionnaire, were higher in the sham rTMS group compared to the active rTMS group, but this difference was not corroborated by cognitive tests. Conclusions rTMS could be used to enhance the efficacy of ECT in patients with TRD. ClinicalTrials.gov: NCT02830399.

Repetitive transcranial magnetic stimulation for the treatment of obsessive compulsive disorder: a double-blind controlled investigation

2007 ◽  
Vol 37 (11) ◽  
pp. 1645-1649 ◽  
Author(s):  
PERMINDER S. SACHDEV ◽  
COLLEEN K. LOO ◽  
PHILIP B. MITCHELL ◽  
TARA F. McFARQUHAR ◽  
GIN S. MALHI
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Obsessive Compulsive Disorder ◽  
Magnetic Stimulation ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Controlled Study ◽  
Treatment Resistant ◽  
Obsessive Compulsive ◽  
Double Blind ◽  
Compulsive Disorder ◽  
Dorsolateral Prefrontal

ABSTRACTBackgroundTo determine the efficacy and tolerability of repetitive transcranial magnetic stimulation (rTMS) as a treatment for obsessive compulsive disorder (OCD) in a double-blind placebo-controlled study.MethodSubjects with treatment-resistant OCD were randomized to rTMS (n=10) or sham rTMS (n=8) for 10 sessions of daily stimulation over the left dorsolateral prefrontal cortex (DLPFC), with subjects and raters being blind to the treatment. Subjects were offered an open extension of up to 20 sessions of rTMS.ResultsThe two groups did not differ on change in Yale–Brown Obsessive Compulsive Scale (YBOCS) or Maudsley Obsessive-Compulsive Inventory scores over 10 sessions, with or without correction for depression ratings. Over 20 sessions, there was a significant reduction in total YBOCS scores, but not after controlling for depression. rTMS over 20 sessions was well tolerated.ConclusionTwo weeks of rTMS over the left DLPFC is ineffective for treatment-resistant OCD.

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