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Longer-term open-label study of adjunctive riluzole in treatment-resistant depression.
Sakurai, H, Dording, C, Yeung, A, Foster, S, Jain, F, Chang, T, Trinh, NH, Bernard, R, Boyden, S, Iqbal, SZ, et al
Journal of affective disorders. 2019;:102-108
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Abstract
BACKGROUND While riluzole has been investigated for the treatment of depression, little is known about its longer-term efficacy and optimal treatment duration in treatment-resistant depression (TRD). The objective of this study is to characterize the longer-term outcome of adjunctive riluzole therapy for TRD in an open-label extension of an 8-week acute treatment trial. METHODS The data from 66 patients with TRD who received adjunctive riluzole in a 12-week open-label extension phase were analyzed. Response rates (⩾50% reduction in the Mongomery-Asberg Depression Rating Scale [MADRS] score), relapse rates (a MADRS score of ⩾22 in patients who had previously achieved response), and adverse events were examined in patients who had achieved response at the end of the acute phase and those who had not. RESULTS Among acute phase responders, the maintained response rate was 66.7% (8/12) and the relapse rate was 8.3% (1/12). In acute phase non-responders, the response rate was 24.1% (13/54). The most commonly reported adverse event was fatigue (9.1%). Three cases were considered serious adverse events; vomiting (n = 1), shortness of breath (n = 1), and aborted suicide attempt (n = 1). LIMITATIONS This longer-term study was open-label and uncontrolled. The sample size was relatively small. CONCLUSIONS Longer-term adjunctive riluzole appears relatively well tolerated and beneficial for maintaining previous response. Additionally, approximately one fourth of patients who did not respond to 8-week antidepressant treatment might respond if treated with riluzole for 12 weeks. Those findings warrant further investigation because adjunctive riluzole could represent an option for treatment of depression when standard antidepressants have failed.
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Selected factors determining a way of coping with stress in type 2 diabetic patients.
Sobol-Pacyniak, AB, Szymczak, W, Kwarta, P, Loba, J, Pietras, T
BioMed research international. 2014;:587823
Abstract
OBJECTIVES The aim of the study was to examine factors which determine stress coping styles in type 2 diabetic (T2D) patients, with regard to selected demographic variables, clinical diabetes-related variables and selected psychical variables (anxiety level and assessment of depressive disorders). METHODS 50 T2D patients, aged 59.9 ± 10.2 years were assessed by Coping Inventory for Stressful Situations (CISS), Spielberger State-Trait Anxiety Inventory (STAI), and Beck Depression Inventory (BDI). In the statistical analysis simple and multivariable logistic regression models were used. RESULTS Variables significantly increasing the selection risk of stress coping style different from preferred task-oriented strategy in a simple logistic regression model are: hypoglycemia within three months prior to the research: odds ratio (OR) = 6.86 (95% confidence interval (CI) 1.25-37.61), taking antidepressants or neuroleptics: OR =15.42 (95% CI 2.42-98.33), severe depression in Beck's scale: OR = 84.00 (95% CI 6.51-1083.65), high state-anxiety level: OR = 9.60 (95% CI 1.08-85.16), and high trait-anxiety level: OR = 18.40 (95%CI 2.96-114.31), but in a multivariable model, diagnosed depression is the strongest factor: OR = 32.38 (95% CI 4.94-212.13). CONCLUSIONS In T2D patients, the strategy to cope with stress appears to be mostly influenced by psychical predisposition.
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Comparison of adjunctive use of aripiprazole with bupropion or selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors: analysis of patients beginning adjunctive treatment in a 52-week, open-label study.
Clayton, AH, Baker, RA, Sheehan, JJ, Cain, ZJ, Forbes, RA, Marler, SV, Marcus, R, Berman, RM, Thase, ME
BMC research notes. 2014;:459
Abstract
BACKGROUND This post hoc analysis assessed the safety, tolerability and effectiveness of long-term treatment with aripiprazole adjunctive to either bupropion or selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs) in patients with major depressive disorder (MDD). METHODS Data from de novo patients (did not participate in 2 previous studies) in a 52-week, open-label safety study of adjunctive aripiprazole after documented inadequate response to 1-4 antidepressant treatments (ADTs; SSRI, SNRI, or bupropion) were analyzed post hoc. Assessments included safety and tolerability, sexual functioning (Massachusetts General Hospital Sexual Functioning Inventory [MGH-SFI]) and Clinical Global Impressions-Severity (CGI-S). RESULTS Forty-seven patients received bupropion plus aripiprazole and 245 received an SSRI/SNRI plus aripiprazole; 19 (40.4%) and 78 (31.8%), respectively, completed 52 weeks of treatment, and 46 and 242, respectively, received ≥1 dose of study medication (safety sample). Median time to discontinuation (any reason) was 184.0 days. Overall, 97.8% of patients in the bupropion group and 93.8% in the SSRI/SNRI group experienced ≥1 adverse event. The most common treatment-emergent adverse events were fatigue (26.1%) and somnolence (21.7%) with bupropion and fatigue (23.6%) and akathisia (23.6%) with an SSRI/SNRI. Mean change in body weight at week 52 (observed cases) was +3.1 kg for bupropion and +2.4 kg for an SSRI/SNRI. Treatment-emergent, potentially clinically relevant abnormalities in fasting glucose occurred in 8.3% of patients with bupropion and 17.4% with an SSRI/SNRI; for abnormalities in fasting total cholesterol, the incidence was 25.0% and 34.7%, respectively. Mean (SE) change from baseline in fasting glucose was 1.4 (1.9) mg/dL with bupropion and 2.7 (1.5) mg/dL with an SSRI/SNRI. Baseline MGH-SFI item scores indicated less severe impairment with bupropion versus an SSRI/SNRI; in both groups most MGH-SFI items exhibited improvement at week 52. Mean CGI-S improvement at week 52 (last observation carried forward) was -1.4 with bupropion and -1.5 with an SSRI/SNRI (efficacy sample). CONCLUSIONS There were no unexpected AEs with long-term adjunctive aripiprazole therapy when added to either bupropion or SSRIs/SNRIs, and symptom improvement was similar between ADT groups. Sexual functioning in patients with MDD on antidepressants was also modestly improved after adding aripiprazole. TRIAL REGISTRATION ClinicalTrials.gov: NCT00095745 (November 9, 2004).
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Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-aspartate antagonist in patients with treatment-resistant major depressive disorder.
DiazGranados, N, Ibrahim, LA, Brutsche, NE, Ameli, R, Henter, ID, Luckenbaugh, DA, Machado-Vieira, R, Zarate, CA
The Journal of clinical psychiatry. 2010;(12):1605-11
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Abstract
OBJECTIVE Suicidal ideation is a medical emergency, especially when severe. Little research has been done on pharmacologic interventions that could address this problem. Ketamine, an N-methyl-D-asparate antagonist, has been reported to have antidepressant effects within hours. We examined the effects of a single dose of ketamine on suicidal ideation in subjects with treatment-resistant major depressive disorder (MDD). METHOD Thirty-three subjects with DSM-IV-diagnosed MDD received a single open-label infusion of ketamine (0.5 mg/kg) and were rated at baseline and at 40, 80, 120, and 230 minutes postinfusion with the Scale for Suicide Ideation (SSI), the Montgomery-Åsberg Depression Rating Scale, the Hamilton Depression Rating Scale, and the Beck Depression Inventory. The study was conducted between October 2006 and January 2009. RESULTS Suicidal ideation scores decreased significantly on the SSI as well as on the suicide subscales of other rating instruments within 40 minutes; these decreases remained significant through the first 4 hours postinfusion (P < .001). Ten subjects (30%) had an SSI score ≥ 4 at baseline; all these scores dropped below 4 (9 dropped by 40 minutes and 1 by 80 minutes). For those patients with a starting score below 4 on the SSI, only 1 reached a score of 4. Depression, anxiety, and hopelessness were significantly improved at all time points (P < .001). CONCLUSIONS Suicidal ideation in the context of MDD improved within 40 minutes of a ketamine infusion and remained improved for up to 4 hours postinfusion. Future studies with ketamine in suicidal ideation are warranted due to the potential impact on public health. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00088699.
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Preliminary evidence of riluzole efficacy in antidepressant-treated patients with residual depressive symptoms.
Sanacora, G, Kendell, SF, Levin, Y, Simen, AA, Fenton, LR, Coric, V, Krystal, JH
Biological psychiatry. 2007;(6):822-5
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BACKGROUND Excessive glutamatergic neurotransmission may contribute to the pathophysiology of major depressive disorder (MDD). Recent evidence suggests that riluzole and other agents that target glutamate neurotransmission may show antidepressant activity. METHODS Ten patients with treatment-resistant depression had riluzole added to their ongoing medication regimen for 6 weeks, followed by an optional 6-week continuation phase. Depression and anxiety severity were assessed using the Hamilton Depression Rating Scale (HDRS) and the Hamilton Anxiety Rating Scale (HARS). Linear mixed models were used to test for a linear trend in HDRS and HARS scores across time with treatment. RESULTS Subjects' HDRS and HARS scores declined significantly following the initiation of riluzole augmentation therapy. The effect of riluzole was significant at the end of the first week of treatment and persisted for the 12-week duration of the study. CONCLUSIONS These data suggest that riluzole augmentation produces antidepressant and anxiolytic effects in patients with treatment-resistant depression.
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Lithium treatment effects on Myo-inositol in adolescents with bipolar depression.
Patel, NC, DelBello, MP, Cecil, KM, Adler, CM, Bryan, HS, Stanford, KE, Strakowski, SM
Biological psychiatry. 2006;(9):998-1004
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BACKGROUND The neurochemical effects of lithium in adolescents with bipolar disorder largely are unknown. This study used proton magnetic resonance spectroscopy (1H MRS) to identify the in vivo effects of lithium on myo-inositol (mI) concentrations in adolescent bipolar depression. METHODS Twenty-eight adolescents (12-18 years old) with bipolar I disorder, current episode depressed, received open-label lithium 30 mg/kg, adjusted to achieve serum levels of 1.0-1.2 mEq/L. The mI concentrations in the medial as well as the left and right lateral prefrontal cortices were measured at baseline, day 7, and day 42 of treatment. Changes in mI concentrations over time were analyzed. RESULTS Significant main effects of time were observed for mI concentrations in the medial (p = .03) and right lateral (p = .05) prefrontal cortices. Baseline concentrations of mI were not significantly different from day 7 or day 42 concentrations. However, mI concentrations on day 42 were significantly higher than those on day 7 (p = .02) in both regions. CONCLUSIONS This study demonstrates that prefrontal mI concentrations do not significantly change from baseline after acute and chronic lithium treatment in adolescents with bipolar depression. Further investigation of the effect of lithium on mI is warranted to better understand possible mechanisms by which lithium exerts antidepressant activity.
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Effect of zinc supplementation on antidepressant therapy in unipolar depression: a preliminary placebo-controlled study.
Nowak, G, Siwek, M, Dudek, D, Zieba, A, Pilc, A
Polish journal of pharmacology. 2003;(6):1143-7
Abstract
A growing body of evidence implicates a derangement of zinc homeostasis in mood disorders. In general, unipolar depression is connected with low blood zinc levels that are increased by effective antidepressant therapy. A placebo-controlled, double blind pilot study of zinc supplementation in antidepressant therapy was conducted in patients who fulfilled DSM IV criteria for major (unipolar) depression. Patients received zinc supplementation (6 patients; 25 mg of Zn2+ once daily) or placebo (8 patients) and were treated with standard antidepressant therapy (tricyclic antidepressants, selective serotonin reuptake inhibitors). Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI) were used to assess efficacy of antidepressant therapy, and patients' status was evaluated before the treatment and 2, 6 and 12 weeks after its commencement. Antidepressant treatment significantly reduced HDRS scores by the 2nd week of treatment in both groups, and lowered BDI scores at the 6th week in zinc-treated group. Zinc supplementation significantly reduced scores in both measures after 6- and 12-week supplementation when compared with placebo treatment. This preliminary study is the first demonstration of the benefit of zinc supplementation in antidepressant therapy. The mechanism(s) may be related to modulation of glutamatergic or immune systems by zinc ion.
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Preliminary randomized double-blind placebo-controlled trial of tryptophan combined with fluoxetine to treat major depressive disorder: antidepressant and hypnotic effects.
Levitan, RD, Shen, JH, Jindal, R, Driver, HS, Kennedy, SH, Shapiro, CM
Journal of psychiatry & neuroscience : JPN. 2000;(4):337-46
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Abstract
OBJECTIVE Because the initial phase of treatment of depression with a selective serotonin reuptake inhibitor is often complicated by a delayed onset of action of the antidepressant or severe insomnia or both, we investigated whether tryptophan, an amino acid with both antidepressant-augmenting and hypnotic effects, would benefit patients with depression at the beginning of treatment with fluoxetine. DESIGN Randomized, double-blind, placebo-controlled trial. PATIENTS Thirty individuals with major depressive disorder. INTERVENTIONS Treatment over 8 weeks with 20 mg of fluoxetine per day and either tryptophan (2 to 4 g per day) or placebo. OUTCOME MEASURES Mood was assessed using the 29-item Hamilton Depression Rating Scale (HDRS-29) and the Beck Depression Inventory (BDI). Laboratory sleep studies were done at baseline and after 4 and 8 weeks of treatment using standard procedures. RESULTS During the first week of treatment, there was a significantly greater decrease in HDRS-29 depression scores, and a similar trend in BDI scores, in the tryptophan/fluoxetine group than in the placebo/fluoxetine group. No significant differences were noted at later time points. With respect to sleep measures, there was a significant group-by-time interaction for slow-wave sleep at week 4. Further analysis revealed a significant decrease in slow-wave sleep after 4 weeks of treatment in the placebo/fluoxetine group, but not in the tryptophan/fluoxetine group. No cases of serotonin syndrome occurred, and the combination was well tolerated, although the 4 g per day dosage of tryptophan produced daytime drowsiness. CONCLUSIONS Combining 20 mg of fluoxetine with 2 g of tryptophan daily at the outset of treatment for major depressive disorder appears to be a safe protocol that may have both a rapid antidepressant effect and a protective effect on slow-wave sleep. Further large-scale studies are needed to confirm these initial findings.