Augmentation Strategy In Patients Research Articles

Augmentation with prazosin for patients with depression and a history of trauma: A randomised, double-blind, placebo-controlled study.

Depression with a history of trauma often responds poorly to conventional antidepressants and has a poor prognosis. Prazosin, an α1-adrenoceptor blocker, has shown promise in treating post-traumatic stress disorder symptoms, particularly nightmares. Its potential in treating depression with trauma history warrants investigation. This randomised, double-blind, placebo-controlled study aimed to investigate the efficacy and tolerability of low-dose prazosin (0.5-1 mg/day) as an augmentation strategy in patients with depression and a history of trauma. We sought to determine if prazosin could provide rapid symptom improvement and enhance overall treatment response compared to placebo in this difficult-to-treat patient population. This randomised, double-blind, placebo-controlled clinical study included 59 patients with first-episode or recurrent unipolar or bipolar depression. After basic antidepressant treatment, they were randomly assigned to a prazosin (0.5-1 mg/day) or placebo group for a 6-week double-blind controlled study. The Montgomery-Åsberg Depression Rating Scale, 17-item Hamilton Depression Scale (HAMD-17), and Hamilton Anxiety Scale (HAMA) were used to evaluate efficacy. There were no significant differences in the results of the demographic and clinical symptom assessment between the two groups (p > 0.05). The difference between the HAMD-17 and HAMA scores was statistically significant after 3 days of treatment (p < 0.05). The difference in response rate between the two groups was statistically significant after week 4 of treatment (end of week 4, 56.7% vs. 24.1%, p = 0.011; end of week 6, 80.0% vs. 48.3%, p = 0.011). The incidence of adverse reactions in the prazosin and placebo groups was 20.0% and 24.1%, respectively, with no statistically significant differences (p > 0.05); however, the prazosin group had a lower incidence of sleeplessness or nightmares (3.3% vs. 20.7%, p = 0.039) but a higher incidence of orthostatic hypotension (16.7% vs. 0%, p = 0.007). The severity of orthostatic hypotension was mild to moderate. Low-dose prazosin can effectively improve the emotional symptoms of patients with depression and a history of trauma, and the common adverse reaction is mild-to-moderate orthostatic hypotension. ChiCTR2200063642.

Study Assessing Use of Mood Stabilizers (Sodium Valproate and Oxcarbazepine) as an Augmentation Strategy in Patients of Treatment-resistant Depression

Study Assessing Use of Mood Stabilizers (Sodium Valproate and Oxcarbazepine) as an Augmentation Strategy in Patients of Treatment-resistant Depression

Efficacy and Safety of Adjunctive Serotonin-Dopamine Activity Modulators in Major Depression: A Meta-Analysis of Randomized Controlled Trials.

Serotonin-dopamine activity modulators (SDAMs) have been approved as an adjunctive treatment to antidepressants in patients with inadequate response. These drugs have been proposed to have a beneficial effect on cognition, sleep-related problems, and other affective symptoms in patients with depression. Previous studies have shown inconsistent evidence and have not reported a pooled effect of the 2 drugs of this class: aripiprazole and brexpiprazole. This meta-analysis evaluated the effect of augmentation with SDAM drugs in patients with major depression. The meta-analysis protocol was made as per Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol guidelines and registered in the International Prospective Register of Ongoing Systematic Reviews. The PubMed/MEDLINE, Cochrane Clinical Trial registry, and EudraCT databases were searched with prespecified search terms. A random-effects meta-analysis was performed using the meta package in R software. Fifteen studies were included in this meta-analysis. The random-effects model analysis observed a pooled effect of 1.55 (95%CI, 1.32-1.84; prediction interval, 0.95-2.55, z = 5.19 [P < .0001]) for remission between the SDAM and placebo groups. A pooled effect of 1.58 (95%CI, 1.37-1.83; prediction interval, 1.00-2.51, z = 6.34 [P<.0001]) for adverse events and 0.72 (95%CI, 0.48-1.08; prediction interval, 0.46-1.12; z = -1.58 [P = .113]) for serious adverse events was observed. No significant publication bias was noticed. The quality of the evidence was rated as high. Adjunct SDAM increased remission in patients and had no significant effect on serious adverse events compared to placebo. Therefore, we conclude that SDAM drugs can be an effective and safe antidepressant augmentation strategy in patients with major depressive disorder.

Comparative study of effectiveness of augmentation with ECT in clozapine resistant schizophrenia (CRS) and non-clozapine resistant schizophrenia (Non-CRS)

Background There is limited evidence for different treatment strategies in patients with clozapine resistant schizophrenia (CRS). Aim To determine the effectiveness of ECT in patients with clozapine resistant schizophrenia and compare the same with a group of patients with non-clozapine resistant schizophrenia, receiving ECT. Results Out of a total of 68 patients with schizophrenia, 27 (38.66%) of patients had CRS. With 6 ECTs, there was a significant reduction in PANSS positive, negative, general psychopathology, prosocial score and depression symptoms in the CRS (p < 0.001) and Non-CRS group (p < 0.001), but no statistically significant difference was seen between the 2 groups in terms of proportion of patients showing >40% response on PANSS total score. The reduction in PANSS score of >40% in CRS group was seen in 48.1% of patients in the positive symptoms subscale, in 25.9% of patients in negative symptoms subscale, in 46.7% of cases in the general psychopathology subscale, in 44.4% of the patients in Depression subscale, in 29.6% of the patients in the modified prosocialsubscaleand in 29.6% of the patients in total PANSS score. Conclusion ECT is an effective augmentation strategy for patients with CRS and it is as effective as when used in patients with non-CRS.

Treatment of Clozapine Nonresponders

Significant proportions of patients with treatment-resistant schizophrenia (TRS) do not respond to clozapine and are known as clozapine nonresponders or ultra-resistant schizophrenia. They are among the most difficult patients to treat. This article attempts to review the available evidence for management of patients with schizophrenia, who do not respond adequately to clozapine and require augmentation of clozapine with another treatment strategy. Many treatment strategies have been evaluated for management of this group of patients. Commonly used pharmacological augmentation strategies which have been evaluated include addition of a second antipsychotic, mood stabilizer, and antidepressant. Other pharmacological agents such as memantine, donepezil, amino acids, omega-3 fatty acids etc. have also been tried. Among the somatic treatments, electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS) have also been evaluated. Non-pharmacological strategies such as cognitive behavior therapy and occupational therapy have also been evaluated clozapine non-response cases. However, at the present, the data is limited to small sample size studies and is not sufficient to make any specific recommendation. Among the various strategies evaluated, ECT is possibly the most effective augmentation strategy in patients not responding or partially responding to clozapine. Among the various pharmacological agents, if the target is positive symptoms, then one of the second-generation antipsychotic like amisulpride or aripiprazole may be considered. If the target is negative symptoms, then amisulpride, mirtazapine, lamotrigine, fluvoxamine, and memantine may be considered. However, it is important to remember that use of combination is associated with more side effects and the patients must be closely monitored. If the patients do not respond to combination, then the same must be abandoned after 3–6 months.

Adjunctive simvastatin for treatment-resistant depression: study protocol of a 12-week randomised controlled trial.

A third of patients diagnosed with major depressive disorder (MDD) experience treatment-resistant depression (TRD). Relatively few pharmacological agents have established efficacy for TRD. Therefore, the evaluation of novel treatments for TRD is a pressing priority. Statins are pleiotropic agents and preclinical studies as well as preliminary clinical trials have suggested that these drugs may have antidepressant properties.AimsTo report on a protocol for a 12-week, randomised, double-blind, placebo-controlled trial of add-on treatment with simvastatin for patients meeting DSM-5 criteria for MDD who have failed to respond to at least two adequate trials with approved antidepressants. The trial has been registered with Clinicaltrials.gov in (ClinicalTrials.gov identifier: NCT03435744). After screening and randomisation to the two parallel arms of the trial, 75 patients will receive simvastatin and 75 patients will receive placebo as adjuncts to treatment as usual. The primary outcome is change in Montgomery-Åsberg Depression Rating Scale scores from baseline to week 12 and secondary outcomes include changes in scores on the 24-item Hamilton Rating Scale for Depression, the Clinical Global Impression scale, the 7-item Generalized Anxiety Disorder scale and change in body mass index from baseline to week 12. Assessments will take place at screening, baseline, and weeks 2, 4, 8 and 12. Checklists for adverse effects will be undertaken at each visit. Simvastatin (20 mg) will be given once daily. Other secondary outcomes include C-reactive protein and plasma lipids measured at baseline and week 12. This trial will assess simvastatin's efficacy and tolerability as an add-on treatment option for patients with TRD and provide insights into its putative mechanisms of action. As the first trial investigating the use of simvastatin as an augmentation strategy in patients with TRD, if the results indicate that adjuvant simvastatin is efficacious in reducing depressive symptoms, it will deliver immediate clinical benefit.Declaration of interestI.B.C. and N.H. have given lectures and advice to Eli Lilly, Bristol Myers Squibb, Lundbeck, Astra Zeneca and Janssen pharmaceuticals for which they or their employing institution have been reimbursed. R.R. and M.M.H. have received educational grants and support for academic meetings from Pfizer, Roche, Novartis and Nabiqasim. A.H.Y. has been commissioned to provide lectures and advice to all major pharmaceutical companies with drugs used in affective and related disorders. A.H.Y. has undertaken investigator-initiated studies from Astra Zeneca, Eli Lilly, Lundbeck and Wyeth. None of the companies have a financial interest in this research.

Efficacy of electroconvulsive therapy augmentation for partial response to clozapine: a pilot randomized ECT – sham controlled trial

Abstract Background Thirty percent of schizophrenia patients are treatment-resistant. Objective This is a single-blinded sham-controlled trial to assess the efficacy of electroconvulsive therapy (ECT) as augmentation strategy in patients with clozapine-resistant schizophrenia. Methods Twenty three subjects were randomly assigned to 12 sessions of ECT (N = 13) or placebo (Sham ECT) (N = 10). The primary outcome was improvement on psychotic symptoms as measured by the mean reduction of the PANSS positive subscale. The assessments were performed by blind raters. Results At baseline both groups were similar, except for negative and total symptoms of the PANSS, which were higher in the Sham group. At the endpoint both groups had a significant decrease from basal score. In the ECT group the PANSS total score decreased 8.78%, from 81.23 to 74.75 (p = 0.042), while the positive subscale had a mean reduction of 19% (19.31 to 16.17, p = 0.006). In the Sham group, the mean reduction of PANSS total score was 15.27% (96.80 to 87.43; p = 0.036), and the PANSS positive subscale decreased 27.81% (22.90 to 19.14, p = 0.008). The CGI score in ECT group decreased 23.0% (5.23 to 4.17; p = 0.001) and decreased 24.31% in the Sham ECT group (5.80 to 4.86; p = 0.004). Discussion In this pilot study, we found no difference between the groups.

Ondansetron augmentation in patients with obsessive-compulsive disorder who are inadequate responders to serotonin reuptake inhibitors: Improvement with treatment and worsening following discontinuation

Object: The aim of this study was to evaluate low-dose ondansetron as an augmentation strategy in patients with obsessive-compulsive disorder (OCD) who do not adequately respond to serotonin reuptake inhibits (SRIs). Methods: Twenty-one OCD patients who had not responded adequately to an SRI received 12 weeks of single-blind ondansetron augmentation initiated at 0.25mg BID for 2 weeks, and titrated to 0.5mg BID for an additional 10 weeks. Patients were rated every two weeks using the Yale–Brown Obsessive Compulsive Scale (YBOCS) and Clinical Global Impressions Scale (CGI). Treatment response was defined as an additional 25% reduction in YBOCS score from the score at the initiation of ondansetron augmentation, an end of treatment YBOCS score of ≤24 and a CGI-Improvement (CGI-I) score of ≤2. Upon completion of treatment course patients were followed for 4 weeks. Results: At week 12, twelve of the 21 (57%) patients were responders. The average reduction in the YBOCS score for the overall group was 27.2%. Responders had an average 44% YBOCS score reduction and 76.9% CGI-I reduction. After discontinuation of ondansetron the YBOCS worsened an average of 15.5% in the entire sample and 38.3% in the responder subsample. No clinically meaningful side effects were reported. Conclusion: OCD patients who do not adequately respond to an SRI may benefit from augmentation with a low-dose of ondansetron. This may provide an alternative approach to augmentation with atypical antipsychotic agents, with a more favorable safety profile.

Comparison of health-related quality of life among patients using atypical antipsychotics for treatment of depression: results from the National Health and Wellness Survey

BackgroundUse of atypical antipsychotics (AA) in combination with an antidepressant is recommended as an augmentation strategy for patients with depression. However, there is a paucity of data comparing aripiprazole and other AAs in terms of patient reported outcomes. Therefore, the objective of this study was to examine the levels of HRQoL and health utility scores in patients with depression using aripiprazole compared with patients using olanzapine, quetiapine, risperidone and ziprasidone.MethodsData were obtained from the 2009, 2010, and 2011 National Health and Wellness Survey (NHWS), a cross-sectional, internet-based survey that is representative of the adult US population. Only those patients who reported being diagnosed with depression and taking an antidepressant and an atypical antipsychotic for depression were included. Patients taking an atypical antipsychotic for less than 2 months or who reported being diagnosed with bipolar disorder or schizophrenia were excluded. Patients taking aripiprazole were compared with patients taking other atypical antipsychotics. Health-related quality of life (HRQoL) and health utilities were assessed using the Short Form 12-item (SF-12) health survey. Differences between groups were analyzed using General Linear Models (GLM) controlling for demographic and health characteristics.ResultsOverall sample size was 426 with 59.9% taking aripiprazole (n = 255) and 40.1% (n = 171) taking another atypical antipsychotic (olanzapine (n = 19), quetiapine (n = 127), risperidone (n = 14) or ziprasidone (n = 11)). Of the SF-12 domains, mean mental component summary (MCS) score (p = .018), bodily pain (p = .047), general health (p = .009) and emotional role limitations (p = .009) were found to be significantly higher in aripiprazole users indicating better HRQoL compared to other atypical antipsychotics. After controlling for demographic and health characteristics, patients taking aripiprazole reported significantly higher mean mental SF-12 component summary (34.10 vs. 31.43, p = .018), bodily pain (55.19 vs. 49.05, p = .047), general health (50.05 vs. 43.07, p = .009), emotional role limitations (49.44 vs. 41.83, p = .009), and SF-6D utility scores (0.59 vs. 0.56, p = .042).ConclusionsComparison of patients taking aripiprazole with a cohort of patients using another AA for depression demonstrated that aripiprazole was independently associated with better (both statistically and clinically) HRQoL and health utilities.

Nicotinic Antagonist Augmentation of Selective Serotonin Reuptake Inhibitor-Refractory Major Depressive Disorder

There is evidence for nicotinic hypercholinergic mechanisms in depression. Clinical relationships between tobacco use and depression suggest important effects of nicotine in major depressive disorder (MDD). It has been hypothesized that cigarette smoking may exert antidepressant effects, presumably mediated through stimulation of nicotinic acetylcholine receptor systems. We compared the nicotinic antagonist, mecamylamine hydrochloride (MEC), with placebo as an augmentation strategy for patients with MDD who were refractory to selective serotonin reuptake inhibitor (SSRI) treatment. Twenty-one SSRI-treated subjects with MDD were randomized to MEC (up to 10 mg/d; n = 11) or placebo (PLO group; n = 10) during an 8-week trial. The primary outcome measure was the change in depressive symptoms assessed using the 17-item Hamilton Depression Rating Scale during the 8-week trial. There was a significant reduction in 17-item Hamilton Depression Rating Scale scores in the MEC versus PLO groups, as evidenced by a significant medication x time interaction (F1,19 = 6.47, P < 0.05). Five (45.5%) of 11 subjects in the active study medication group demonstrated a 50% or more decrease in depressive symptoms from baseline as compared with 1 (10%) of 10 subjects assigned to placebo medication, but this difference was not significant (P = 0.15; Fisher exact test). The primary side effects of MEC were constipation and orthostatic hypotension. These preliminary findings suggest that the nicotinic acetylcholine receptor antagonist, MEC, may have utility as an augmentation strategy for patients with SSRI-refractory MDD.

TREAD: TReatment with Exercise Augmentation for Depression: study rationale and design

Despite recent advancements in the pharmacological treatment of major depressive disorder (MDD), over half of patients who receive treatment with antidepressant medication do not achieve full remission of symptoms. There is evidence that exercise can reduce depressive symptomatology when used as a treatment for MDD. However, no randomized controlled trials have evaluated exercise as an augmentation strategy for patients with carefully diagnosed MDD who remain symptomatic following an adequate acute phase trial of antidepressant therapy. TReatment with Exercise Augmentation for Depression (TREAD) is an NIMH-funded, randomized, controlled trial designed to assess the relative efficacy of two doses of aerobic exercise to augment selective serotonin reuptake inhibitor (SSRI) treatment of MDD. The TREAD study includes 12 weeks of acute phase treatment with a 12-week post-treatment follow-up. In addition to looking at change in depressive symptoms as a primary outcome, it also includes comprehensive assessment of psychosocial function and treatment adherence. This paper reviews the rationale and design of TREAD and illustrates how we address several key issues in contemporary patient-oriented research on MDD: 1) the use of augmentation strategies in the treatment of depressive disorders in general, 2) the use of non-pharmacological strategies in the treatment of depressive disorders, 3) the considerations of designing a well-controlled trial using two active treatment groups, and 4) the implementation of an adherence program for the use of exercise as a treatment strategy. The TREAD study is uniquely designed to overcome sources of potential bias and threats to internal and external validity that have limited prior research on the mental health effects of exercise. The study is facilitated by the development of a multidisciplinary research team that includes experts in both depression treatment and exercise physiology, as well as other related fields.

Lamotrigine Augmentation Strategy for Patients with Treatment-Resistant Depression

To investigate if lamotrigine added to an antidepressant regimen reduces the symptoms of major depression in treatment-resistant patients. Charts were retrospectively reviewed for 34 patients (36-63 years of age) with major depressive disorder who received lamotrigine augmentation to the antidepressant regimen for treatment-resistant depression (TRD). Data collection occurred at baseline and at an average of 30 (Time 2), 78 (Time 3), 167 (Time 6), and 356 days (Time 12), thereafter, using a "Medication Visit by MD" scale for collection of target symptom data at each timepoint. Following the addition of lamotrigine to the antidepressant regimen (mean dose of 43, 63, and 113 mg/day for Time 3, Time 6, and Time 12, respectively), a statistically significant reduction of scores was shown as early as Time 2 for target symptoms of depressed mood, loss of interest, anxiety, irritability, (low) energy, and cognitive impairment. The difference from baseline remained statistically significant at Time 3, Time 6, and Time 12 (with the exception of irritability, which was not statistically significant at Time 6). "Patient's response" also reflected statistically significant improvement at each time period compared with baseline. The most common side effect reported and reason for discontinuation was tiredness. Because TRD is a clinical condition that can present with severe and disabling symptoms, many clinicians are faced with an urgent need to find relief for their patients. Trying to achieve symptom improvement in a timely manner during a medication change can be challenging and difficult. This can be managed by an augmentation strategy using a psychotropic add-on to an existing medication regimen. Our results show the benefits of lamotrigine augmentation to an antidepressant regimen. Prospective, controlled clinical trials with larger sample size are needed to confirm our results. In this retrospective chart review, augmentation with lamotrigine was a tolerable and efficacious strategy for treating patients with TRD.