Placebo-Controlled Trial of Lithium Augmentation of Fluoxetine and Lofepramine

1995 ◽  
Vol 166 (1) ◽  
pp. 80-86 ◽  
Author(s):  
Cornelius L. E. Katona ◽  
Mohammed T. Abou-Saleh ◽  
Deborah A. Harrison ◽  
Bertrand A. Nairac ◽  
Denzil R. L. Edwards ◽  
...  
Keyword(s):  
Rating Scale ◽  
Antidepressant Treatment ◽  
Controlled Trial ◽  
Depressive Illness ◽  
Controlled Trials ◽  
Major Depressive ◽  
Double Blind ◽  
Primary Care Settings ◽  
Resistant Depression ◽  
Lithium Augmentation

BackgroundThis study was designed to establish whether (as suggested in a number of open and relatively small controlled trials) lithium augmentation is more effective than continued antidepressant alone, where response to a standard course of antidepressant treatment has been absent or partial.MethodLithium or placebo was added on a double-blind basis for six weeks to the drug regime of 62 patients with major depressive illness (in both hospital and primary care settings) who had failed to respond to a controlled trial of fluoxetine or lofepramine. Response was defined as a final Hamilton Depression Rating Scale (HDRS) score of < 10.ResultsResponse was seen more frequently in patients taking lithium (15/29) than in those remaining on antidepressant alone (8/32; P < 0.05). Rapid response to lithium augmentation (LA) was not consistently observed in this cohort. Mean HDRS scores after six weeks were significantly lower (P < 0.01) in the lithium group after excluding those who had not achieved significant exposure to lithium (arbitrarily defined as two or more lithium levels ≥ 0.4 mmol/1). No differences in the efficacy of LA were apparent between fluoxetine and lofepramine.ConclusionsOur results confirm that LA is a useful strategy in the treatment of antidepressant-resistant depression. Partial response was, however, frequently observed with continued antidepressant treatment alone, and the superiority of LA appears to depend on achieving adequate serum lithium levels.

scholarly journals Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial

2018 ◽  
Vol 49 (4) ◽  
pp. 655-663 ◽  
Author(s):  
Fernanda Palhano-Fontes ◽  
Dayanna Barreto ◽  
Heloisa Onias ◽  
Katia C. Andrade ◽  
Morgana M. Novaes ◽  
...  
Keyword(s):  
Rating Scale ◽  
Remission Rate ◽  
Controlled Trial ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Open Label ◽  
Double Blind ◽  
Therapeutic Value ◽  
Antidepressant Effects ◽  
Resistant Depression

AbstractBackgroundRecent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression.MethodsTo test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing.ResultsWe observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p= 0.04), and at D7 (p< 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen'sd= 0.84; D2: Cohen'sd= 0.84; D7: Cohen'sd= 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64%v.27%;p= 0.04). Remission rate showed a trend toward significance at D7 (36%v.7%,p= 0.054).ConclusionsTo our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered athttp://clinicaltrials.gov(NCT02914769).

Effectiveness of mirtazapine as add-on to paroxetine v. paroxetine or mirtazapine monotherapy in patients with major depressive disorder with early non-response to paroxetine: a two-phase, multicentre, randomized, double-blind clinical trial

2020 ◽  
pp. 1-9 ◽  
Author(s):  
Le Xiao ◽  
Xuequan Zhu ◽  
Amy Gillespie ◽  
Yuan Feng ◽  
Jingjing Zhou ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Rating Scale ◽  
Antidepressant Treatment ◽  
Additional Treatment ◽  
Combination Group ◽  
Open Label ◽  
Major Depressive ◽  
Double Blind ◽  
Early Improvement

Abstract Background This study aimed to examine the efficacy of combining paroxetine and mirtazapine v. switching to mirtazapine, for patients with major depressive disorder (MDD) who have had an insufficient response to SSRI monotherapy (paroxetine) after the first 2 weeks of treatment. Methods This double-blind, randomized, placebo-controlled, three-arm study recruited participants from five hospitals in China. Eligible participants were aged 18–60 years with MDD of at least moderate severity. Participants received paroxetine during a 2-week open-label phase and patients who had not achieved early improvement were randomized to paroxetine, mirtazapine or paroxetine combined with mirtazapine for 6 weeks. The primary outcome was improvement on the Hamilton Rating Scale for Depression 17-item (HAMD-17) scores 6 weeks after randomization. Results A total of 204 patients who showed early non-response to paroxetine monotherapy were randomly assigned to receive either mirtazapine and placebo (n = 68), paroxetine and placebo (n = 68) or mirtazapine and paroxetine (n = 68), with 164 patients completing the outcome assessment. At week 8, the least squares (LS) mean change of HAMD-17 scores did not significantly differ among the three groups, (12.98 points) in the mirtazapine group, (12.50 points) in the paroxetine group and (13.27 points) in the mirtazapine plus paroxetine combination group. Participants in the paroxetine monotherapy group were least likely to experience adverse effects. Conclusions After 8 weeks follow-up, paroxetine monotherapy, mirtazapine monotherapy and paroxetine/mirtazapine combination therapy were equally effective in non-improvers at 2 weeks. The results of this trial do not support a recommendation to routinely offer additional treatment or a switch in treatment strategies for MDD patients who do not show early improvement after 2 weeks of antidepressant treatment.

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

BJPsych Open ◽  
2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Muhammad I. Husain ◽  
Imran B. Chaudhry ◽  
Ameer B. Khoso ◽  
Mohammad Omair Husain ◽  
Raza R. Rahman ◽  
...  
Keyword(s):  
Rating Scale ◽  
Plasma Lipids ◽  
Controlled Trial ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Double Blind ◽  
Treatment As Usual ◽  
Novel Treatments ◽  
Resistant Depression ◽  
Secondary Outcomes

BackgroundA 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).MethodAfter 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.ResultsThis 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.ConclusionsAs 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.

scholarly journals A Double-Blind Pilot Dosing Study of Low Field Magnetic Stimulation (LFMS) for Treatment-Resistant Depression (TRD)

2018 ◽  
Author(s):  
Marc J. Dubin ◽  
Irena Ilieva ◽  
Zhi-De Deng ◽  
Jeena Thomas ◽  
Ashly Cochran ◽  
...  
Keyword(s):  
Magnetic Stimulation ◽  
Rating Scale ◽  
Bipolar Depression ◽  
Controlled Trial ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Double Blind ◽  
The Third ◽  
Low Field ◽  
Resistant Depression

AbstractLow Field Magnetic Stimulation is a potentially rapid-acting treatment for depression with mood-enhancing effects in as little as one 20-minute session. The most convincing data for LFMS has come from treating bipolar depression. We examined whether LFMS also has rapid mood-enhancing effects in treatment-resistant major depressive disorder, and whether these effects are dose-dependent. We hypothesized that a single 20-min session of LFMS would reduce depressive symptom severity and that the magnitude of this change would be greater after three 20-min sessions than after a single 20-min session. In a double-blind randomized controlled trial, 30 participants (age 21–65) with treatment-resistant depression were randomized to three 20-minute active or sham LFMS treatments with 48 hours between treatments. Response was assessed immediately following LFMS treatment using the 6-item Hamilton Depression Rating Scale (HAMD-6), the Positive and Negative Affect Scale (PANAS) and the Visual Analog Scale. Following the third session of LFMS, the effect of LFMS on VAS and HAMD-6 was superior to sham (F(1, 24) = 7.45, p = 0.03, Holm-Bonferroni corrected; F(1,22) = 6.92, p = 0.03, Holm-Bonferroni corrected, respectively). There were no differences between sham and LFMS following the initial or second session with the effect not becoming significant until after the third session. Three 20-minute LFMS sessions were required for active LFMS to have a mood-enhancing effect for individuals with treatment-resistant depression. As this effect may be transient, future work should address dosing schedules of longer treatment course as well as biomarker-based targeting of LFMS to optimize patient selection and treatment outcomes.

scholarly journals A randomized placebo-controlled trial on the antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression

2017 ◽  
Author(s):  
Fernanda Palhano-Fontes ◽  
Dayanna Barreto ◽  
Heloisa Onias ◽  
Katia C Andrade ◽  
Morgana Novaes ◽  
...  
Keyword(s):  
Rating Scale ◽  
Remission Rate ◽  
Controlled Trial ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Open Label ◽  
Double Blind ◽  
Therapeutic Value ◽  
Antidepressant Effects ◽  
Resistant Depression

AbstractRecent open label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression. In order to further test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. Changes in depression severity were assessed with the Montgomery–Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale (HAM-D). Assessments were made at baseline, and at one (D1), two (D2) and seven (D7) days after dosing. We observed significant antidepressant effects of ayahuasca when compared to placebo at all timepoints. MADRS scores were significantly lower in the ayahuasca group compared to placebo (at D1 and D2: p=0.04; and at D7: p<0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen’ s d=0.84; D2: Cohen’ s d=0.84; D7: Cohen’ s d=1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% vs. 27%; p=0.04), while remission rate was marginally significant at D7 (36% vs. 7%, p=0.054). To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression.

scholarly journals Augmentation therapy with minocycline in treatment-resistant depression patients with low-grade peripheral inflammation: results from a double-blind randomised clinical trial

2021 ◽  
Author(s):  
Maria Antonietta Nettis ◽  
Giulia Lombardo ◽  
Caitlin Hastings ◽  
Zuzanna Zajkowska ◽  
Nicole Mariani ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Rating Scale ◽  
Antidepressant Treatment ◽  
Randomised Clinical Trial ◽  
Peripheral Inflammation ◽  
Low Grade ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Double Blind ◽  
Resistant Depression

AbstractThis study aimed to investigate the role of baseline levels of peripheral inflammation when testing the efficacy of antidepressant augmentation with minocycline in patients with treatment-resistant depression. We conducted a 4-week, placebo-controlled, randomised clinical trial of minocycline (200 mg/day) added to antidepressant treatment in 39 patients selected for elevated levels of serum C-reactive protein (CRP ≥ 1 mg/L), n = 18 randomised to minocycline (M) and n = 21 to placebo (P). The main outcome was the change in Hamilton Depression Rating Scale (HAM-D-17) score from baseline to week 4, expressed both as mean and as full or partial response, in the overall sample and after further stratification for baseline CRP≥3 mg/L. Secondary outcomes included changes in other clinical and inflammatory measures. Changes in HAM-D-17 scores and the proportion of partial responders did not differ between study arms. After stratification for CRP levels <3 mg/L (CRP−) or ≥3 mg/L (CRP+), CRP+/M patients showed the largest changes in HAM-D-17 scores (mean ± SD = 12.00 ± 6.45) compared with CRP-/M (2.42 ± 3.20, p < 0.001), CRP+/P (3.50 ± 4.34, p = 0.003) and CRP−/P (2.11 ± 3.26, p = 0.006) patients, and the largest proportion (83.3%, p = 0.04) of partial treatment response at week 4. The threshold point for baseline CRP to distinguish responders from non-responders to minocycline was 2.8 mg/L. Responders to minocycline had higher baseline IL-6 concentrations than non-responders (p = 0.03); IFNγ was significantly reduced after treatment with minocycline compared with placebo (p = 0.03). Our data show some evidence of efficacy of add-on treatment with minocycline in MDD patients but only in those with low-grade inflammation defined as CRP ≥3 mg/L.

Duloxetine in the treatment of major depressive disorder: a placebo- and paroxetine-controlled trial

2006 ◽  
Vol 21 (6) ◽  
pp. 367-378 ◽  
Author(s):  
D.G.S. Perahia ◽  
F. Wang ◽  
C.H. Mallinckrodt ◽  
D.J. Walker ◽  
M.J. Detke
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Acute Phase ◽  
Rating Scale ◽  
Controlled Trial ◽  
Published Data ◽  
Efficacy And Safety ◽  
Major Depressive ◽  
Double Blind ◽  
Efficacy Measures

AbstractObjective:Duloxetine doses of 80 and 120 mg/day were assessed for efficacy and safety in the treatment of major depressive disorder (MDD).Methods:In this randomized, double-blind trial, patients age ≥ 18 meeting DSM-IV criteria for MDD were randomized to placebo (N = 99), duloxetine 80 mg/day (N = 93), duloxetine 120 mg/day (N = 103), or paroxetine 20 mg/day (N = 97). The primary outcome measure was mean change from baseline in the 17-item Hamilton rating scale for depression (HAMD17) total score after 8 weeks of treatment; a number of secondary efficacy measures also were assessed. Safety and tolerability were assessed via collection and analysis of treatment–emergent adverse events (TEAEs), vital signs, and weight. The Arizona sexual experiences scale was used to assess sexual functioning. Patients who had a ≥ 30% reduction from baseline in the HAMD17 total score at the end of the acute phase entered a 6-month continuation phase where they remained on the same treatment as they had taken during the acute phase; efficacy and safety/tolerability outcomes were assessed during continuation treatment.Results:More than 87% of patients completed the acute phase in each treatment group. Duloxetine-treated patients (both doses) showed significantly greater improvement (P < 0.05) in the HAMD17 total score at week 8 compared with placebo. Paroxetine was not significantly different from placebo (P = 0.089) on mean change on the HAMD17. Duloxetine 120 mg/day also showed significant improvement on most secondary efficacy measures (six of nine) compared with placebo while duloxetine 80 mg/day (three of nine) and paroxetine (three of nine) were significantly superior to placebo on fewer secondary measures. HAMD17 mean change data from this study and an identical sister study were pooled as defined a priori for the purposes of performing a non-inferiority test versus paroxetine. Both duloxetine doses met statistical criteria for non-inferiority to paroxetine. TEAE reporting rates were low in all treatment groups and no deaths occurred in the acute or continuation phases.Conclusions:The efficacy of duloxetine at doses of 80 and 120 mg/day in the treatment of MDD was demonstrated. Tolerability, as measured by TEAEs, and safety were similar to paroxetine 20 mg/day and consistent with previous published data on duloxetine in the treatment of MDD.

How Long Should the Elderly Take Antidepressants?

1993 ◽  
Vol 162 (2) ◽  
pp. 175-182 ◽  
Author(s):  
◽  
Robin Jacoby ◽  
A. Daniel Lunn ◽  
M. Ardern ◽  
K. Bergmann ◽  
...  
Keyword(s):  
Relative Risk ◽  
Controlled Trial ◽  
Antidepressant Medication ◽  
The Elderly ◽  
Depressive Illness ◽  
Favourable Outcome ◽  
Elderly Persons ◽  
Major Depressive ◽  
Double Blind ◽  
Risk Of Relapse

Of 219 elderly patients with a major depressive disorder (meeting RDC), 69 recovered sufficiently and consented to enter a two-year double-blind placebo-controlled trial of dothiepin. Survival analysis revealed that dothiepin reduced the relative risk of relapse by two and a half times. Past but not current serious physical illness was also associated with a favourable outcome, whereas a prolonged index depressive illness trebled the relative risk of relapse. In the light of previous research on prognosis it is suggested that elderly persons who recover from a major depressive illness should continue with antidepressant medication for at least two years, if not indefinitely.

Lithium Augmentation Therapy in Tricyclic-Resistant Depression

1993 ◽  
Vol 162 (5) ◽  
pp. 634-640 ◽  
Author(s):  
George Stein ◽  
Morris Bernadt
Keyword(s):  
Low Dose ◽  
Controlled Trial ◽  
Depressive Illness ◽  
Tricyclic Antidepressant ◽  
Antidepressant Effect ◽  
Significant Difference ◽  
Resistant Depression ◽  
Drug Responsiveness ◽  
Experimental Group ◽  
Lithium Augmentation

Thirty-four patients with tricyclic-resistant depressive illness took part in a nine-week, doubleblind, placebo-controlled trial of lithium augmentation. In addition to the maximum tolerated doses of their tricyclic antidepressant, the experimental group (n= 16) received 250 mg lithium daily for three weeks, followed by 750 mg lithium daily for six weeks, while the controls (n= 18) received placebo for three weeks followed by three weeks each of 250 mg lithium daily and 750 mg lithium daily. There was no significant difference between placebo and 250 mg lithium for weeks 0-3 of the trial. However, there was a significantly greater improvement on the MADRS for weeks 3-6 for those subjects on 750 mg lithium than for those on 250 mg lithium. In addition, using a 50% fall in the HRSD as a criterion of drug responsiveness, 22% responded to placebo, 18% to 250 mg lithium, and 44% to 750mg lithium. Thus, lithium in normal, but not in low, dose has a significant antidepressant effect in TCA-resistant depression. Further controlled studies using lithium in normal dose in trials which have a greater duration of placebo exposure are required to confirm the lithium augmentation effect.

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