scholarly journals Clinical Switching Strategies of Various Antidepressants to Vortioxetine in the PREDDICT Trial

2020 ◽  
Author(s):  
Natalie T Mills ◽  
Emma Sampson ◽  
Célia Fourrier ◽  
Bernhard T Baune
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Tricyclic Antidepressants ◽  
Rating Scale ◽  
Antidepressant Medication ◽  
Treatment Resistance ◽  
Baseline Visit ◽  
Noradrenaline Reuptake ◽  
Clinical Trials Registry ◽  
Study Participants ◽  
To Receive

Abstract Background Partial response to antidepressant medication as well as relapse and treatment resistance are common in major depressive disorder (MDD). Therefore, for most patients with MDD, there will be a need to consider changing antidepressant medication at some stage during the course of the illness. The PREDDICT study investigates the efficacy of augmenting vortioxetine with celecoxib. Methods We describe the method used in the PREDDICT study to change participants, who were already taking antidepressant medication at the time of the screening visit, to vortioxetine. We used a cross-titration to change study participants to vortioxetine. Results Of a total of 122 study participants who were randomized to receive vortioxetine plus celecoxib or vortioxetine plus placebo at the study baseline visit, 82 were taking antidepressant medication (other than vortioxetine) prior to randomization. These medications were selective serotonin reuptake inhibitors, serotonin noradrenaline reuptake inhibitors, tricyclic antidepressants, mirtazapine, or agomelatine. Eighty of these 82 participants completed the changeover to vortioxetine as well as the study baseline visit. We found side effects were generally mild during this changeover period. In addition, there was a reduction in mean total Montgomery-Åsberg Depression Rating Scale score of 2.5 (SD 6.0) from study baseline to week 2 and a further reduction in mean total Montgomery-Åsberg Depression Rating Scale of 2.5 (SD 5.9) from week 2 to week 4. Conclusion Changing other antidepressants to vortioxetine can be done safely and was generally well-tolerated. However, there are some antidepressant classes, in particular monoamine oxidase inhibitors that require a washout period, which were not represented in this study. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR); ID number 12617000527369p; http://www.anzctr.org.au/ACTRN12617000527369p.aspx

scholarly journals A comparative study on efficacy of amitriptyline and escitalopram in the treatment of depression

2018 ◽  
Vol 7 (2) ◽  
pp. 234
Author(s):  
Sushant Aryal ◽  
Kajal Chakrabarti ◽  
Mayuri Gupta
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Tricyclic Antidepressants ◽  
Rating Scale ◽  
Antidepressant Medication ◽  
Antidepressant Effect ◽  
Treatment Of Depression ◽  
Intergroup Comparison ◽  
Before And After ◽  
Antidepressant Efficacy ◽  
One Year

Background: Several generations of antidepressant medication which act by distinct pharmacological mechanisms have been introduced for the treatment of depression; tricyclic antidepressants (TCAs) were first line of treatment for many years. However, over the last decade, selective serotonin reuptake inhibitors (SSRIs) have displaced TCAs, mainly because of better side effect profile. There are no references in literature on comparison of efficacy of TCAs and SSRIs in Nepalese population. This study attempted to compare the efficacy of amitriptyline, a reference standard TCA with escitalopram, a newer SSRI in Nepalese population.Methods: An open level, randomised, prospective study was conducted for one year duration. Eighty outpatients suffering from major depression who met inclusion and exclusion criteria were randomly assigned to either amitriptyline or escitalopram group for four week study. Seventy one patients (amitriptyline N: 36, escitalopram N: 35) completed the study. Hamilton Depression Rating Scale (HDRS) was used to measure the antidepressant effect. Antidepressant efficacy was evaluated on reduction of HDRS score before and after therapy (End of four weeks).Results: In amitriptyline group, mean percentage reduction in HDRS score was 58.29% (13.5 points), while in escitalopram group was 60.78% (14.03 points). Both the drugs significantly improved the HDRS score at the end of the study (p<0.05). On intergroup comparison, antidepressant efficacy of amitriptyline and escitalopram did not differ significantly from each other (p>0.05).Conclusions: This study suggests that escitalopram is effective in the treatment of depression and its efficacy appears to be comparable to amitriptyline at the end of four weeks.

Pharmacological Treatments for Unipolar Depression

2007 ◽  
pp. 271-288 ◽  
Author(s):  
Charles B. Nemeroff ◽  
Alan F. Schatzberg
Keyword(s):  
Major Depression ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Rating Scale ◽  
Antidepressant Treatment ◽  
Safety Margin ◽  
Antidepressant Medication ◽  
Unipolar Depression ◽  
Controlled Trials ◽  
Adverse Side Effect ◽  
Drug Induced

The treatment of unipolar major depression with antidepressant medication is well established on the basis of scores of randomized placebo-controlled trials involving thousands of patients. Tricyclic antidepressants (TCAs) were the first to be studied extensively; meta-analyses of placebo-controlled trials show them to be consistently and significantly more efficacious than a placebo. Because of a narrow safety margin and significant drug-induced adverse side effect problems, TCAs have now largely been replaced as the first-line treatment of depression by selective serotonin reuptake inhibitors (SSRIs)—fluoxetine, sertraline, paroxetine, citalopram, and escitalopram; serotonin norepinephrine reuptake inhibitors (SNRIs)—venlafaxine and duloxetine; as well as other compounds, including, for example, bupropion and mirtazapine. Each of these agents has been shown to be superior to a placebo and as effective as comparator TCAs or SSRIs in controlled trials. Clinical trials consistently show them to be better tolerated than TCAs, and they clearly have a wider margin of safety. However, there is a controversy concerning whether TCAs are more effective than SSRIs for the treatment of the most severely ill depressed patients. Monoamine oxidase inhibitors (MAOIs), while also more effective than placebo, have generally been reserved for treatment-refractory patients; however, a recently released transdermally delivered selegiline may be used in less refractory patients. It is now generally recognized that patients with recurrent major depression benefit from continued antidepressant treatment, and there is evidence that TCAs, SSRIs, SNRIs, and so forth are all effective for the long-term management of recurrent major depression. An important issue in evaluating the antidepressant literature is to distinguish between response rated as a reduction in the level of symptoms on a rating scale and response rated as true remission from illness.

scholarly journals Toxicity of antidepressants: rates of suicide relative to prescribing and non-fatal overdose

2010 ◽  
Vol 196 (5) ◽  
pp. 354-358 ◽  
Author(s):  
Keith Hawton ◽  
Helen Bergen ◽  
Sue Simkin ◽  
Jayne Cooper ◽  
Keith Waters ◽  
...  
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Tricyclic Antidepressants ◽  
Case Fatality ◽  
Relative Toxicity ◽  
Toxicity Index ◽  
Undetermined Intent ◽  
Noradrenaline Reuptake ◽  
Poisoning Deaths ◽  
Rate Ratios ◽  
Serotonergic Antidepressant

BackgroundSelf-poisoning is a common method of suicide and often involves ingestion of antidepressants. Information on the relative toxicity of antidepressants is therefore extremely important.AimsTo assess the relative toxicity of specific tricyclic antidepressants (TCAs), a serotonin and noradrenaline reuptake inhibitor (SNRI), a noradrenergic and specific serotonergic antidepressant (NaSSA), and selective serotonin reuptake inhibitors (SSRIs).MethodObservational study of prescriptions (UK), poisoning deaths involving single antidepressants receiving coroners' verdicts of suicide or undetermined intent (England and Wales) and non-fatal self-poisoning episodes presenting to six general hospitals (in Oxford, Manchester and Derby) between 2000 and 2006. Calculation of fatal toxicity index based on ratio of rates of deaths to prescriptions, and case fatality based on ratio of rates of deaths to non-fatal self-poisonings.ResultsFatal toxicity and case fatality indices provided very similar results (rho for relative ranking of indices 0.99). Case fatality rate ratios showed greater toxicity for TCAs (13.8, 95% CI 13.0–14.7) than the SNRI venlafaxine (2.5, 95% CI 2.0–3.1) and the NaSSA mirtazapine (1.9, 95% CI 1.1–2.9), both of which had greater toxicity than the SSRIs (0.5, 95% CI 0.4–0.7). Within the TCAs, compared with amitriptyline both dosulepin (relative toxicity index 2.7) and doxepin (2.6) were more toxic. Within the SSRIs, citalopram had a higher case fatality than the other SSRIs (1.1, 95% CI 0.8–1.4 v. 0.3, 95% CI 0.2–0.4).ConclusionsThere are wide differences in toxicity not only between classes of antidepressants, but also within classes. The findings are relevant to prescribing decisions, especially in individuals at risk, and to regulatory policy.

scholarly journals Polymorphism of the 5-HT transporter and response to antidepressants: randomised controlled trial

2011 ◽  
Vol 198 (6) ◽  
pp. 464-471 ◽  
Author(s):  
Glyn Lewis ◽  
Jean Mulligan ◽  
Nicola Wiles ◽  
Philip Cowen ◽  
Nick Craddock ◽  
...  
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Antidepressant Treatment ◽  
Controlled Trial ◽  
Automated System ◽  
Insertion Polymorphism ◽  
Noradrenaline Reuptake ◽  
Parallel Group ◽  
Personalise Treatment ◽  
Randomised Controlled ◽  
To Receive

BackgroundAntidepressants exhibit a variety of pharmacological actions including inhibition of the serotonin and noradrenaline transporters. We wished to investigate whether genetic variation could be used to target or personalise treatment, in a comparison of selective serotonin reuptake inhibitors (SSRIs) with noradrenaline reuptake inhibitors (NARIs).AimsTo test the hypothesis that patients homozygous for the long (insertion) polymorphism of the serotonin transporter (5-HTTLPR) have an increased response to SSRI antidepressants but not to NARI antidepressants.MethodIn an individually randomised, parallel-group controlled trial, people meeting criteria for a depressive episode who were referred by their general practitioner were randomised to receive either citalopram (an SSRI) or reboxetine (an NARI). Randomisation was by means of a remote automated system accessed by telephone. The main outcome was depressive symptoms, measured by Beck Depression Inventory (BDI) total score 6 weeks after randomisation. The trial was registered with the International Standard Randomised Controlled Trials Number registry (ISRCTN31345163).ResultsAltogether 298 participants were randomised to receive citalopram and 303 were randomised to reboxetine. At 6 weeks follow-up, complete data were available for 258 participants taking citalopram and 262 taking reboxetine. We found no evidence to support an influence of 5-HTTLPR on outcome following antidepressant treatment. The interaction term for BDI score at 6 weeks was 0.50 (95% CI −2.04 to 3.03, P = 0.70), which indicated that responses to the SSRI and NARI were similar irrespective of 5-HTTLPR genotype.ConclusionsIt is unlikely that the 5-HTTLPR polymorphism alone will be clinically useful in predicting response to antidepressants in people with depression.

scholarly journals Alterations in acylcarnitines, amines, and lipids inform about the mechanism of action of citalopram/escitalopram in major depression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Siamak MahmoudianDehkordi ◽  
◽  
Ahmed T. Ahmed ◽  
Sudeepa Bhattacharyya ◽  
Xianlin Han ◽  
...  
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Rating Scale ◽  
Lipid Membrane ◽  
Antidepressant Medication ◽  
Methionine Sulfoxide ◽  
Therapeutic Benefit ◽  
Mechanisms Of Action ◽  
Research Network ◽  
One Carbon Metabolism ◽  
Hamilton Rating Scale

AbstractSelective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder (MDD), yet their mechanisms of action are not fully understood and their therapeutic benefit varies among individuals. We used a targeted metabolomics approach utilizing a panel of 180 metabolites to gain insights into mechanisms of action and response to citalopram/escitalopram. Plasma samples from 136 participants with MDD enrolled into the Mayo Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) were profiled at baseline and after 8 weeks of treatment. After treatment, we saw increased levels of short-chain acylcarnitines and decreased levels of medium-chain and long-chain acylcarnitines, suggesting an SSRI effect on β-oxidation and mitochondrial function. Amines—including arginine, proline, and methionine sulfoxide—were upregulated while serotonin and sarcosine were downregulated, suggesting an SSRI effect on urea cycle, one-carbon metabolism, and serotonin uptake. Eighteen lipids within the phosphatidylcholine (PC aa and ae) classes were upregulated. Changes in several lipid and amine levels correlated with changes in 17-item Hamilton Rating Scale for Depression scores (HRSD17). Differences in metabolic profiles at baseline and post-treatment were noted between participants who remitted (HRSD17 ≤ 7) and those who gained no meaningful benefits (<30% reduction in HRSD17). Remitters exhibited (a) higher baseline levels of C3, C5, alpha-aminoadipic acid, sarcosine, and serotonin; and (b) higher week-8 levels of PC aa C34:1, PC aa C34:2, PC aa C36:2, and PC aa C36:4. These findings suggest that mitochondrial energetics—including acylcarnitine metabolism, transport, and its link to β-oxidation—and lipid membrane remodeling may play roles in SSRI treatment response.

scholarly journals Efficacy and tolerability of milnacipran and escitalopram: a comparative study among patients of depression

2018 ◽  
Vol 7 (5) ◽  
pp. 839
Author(s):  
Meghna Shinde ◽  
Pooja Reddy ◽  
Mohit Kulmi ◽  
Chhaya Goyal
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Rating Scale ◽  
Drop Out ◽  
Comparable Efficacy ◽  
Major Depressive ◽  
Drop Out Rate ◽  
Adverse Experiences ◽  
Noradrenaline Reuptake ◽  
Minimum Score ◽  
Icd 10

Background: The present prospective, open labelled study was designed to evaluate the efficacy and tolerability of escitalopram, selective serotonin reuptake inhibitors (SSRI) in comparison with milnacipran, dual serotonin and noradrenaline reuptake inhibitors (SNRI) in the treatment of major depressive disorder.Methods: Outpatients (N=120) with an ongoing/newly diagnosed ICD-10 major depressive episode and having a minimum score of 8 on the 21-item Hamilton Depression Rating Scale (HDRS) were assigned to escitalopram, 10–20 mg/day (54 patients) and milnacipran 50-100mg (66 patients), for an 8 week treatment period with follow up at 2nd, 4th and 8th week. The parameters for efficacy were improvement (decrease in HDRS scores at 8 weeks from baseline values), response (decrease of ≥50% in the HDRS scores) and remission (HDRS score of ≤7). Tolerability was assessed by comparing the frequency of adverse effects and drop out rate due to the same at the end of 2nd, 4th and 8th week in both the groups.Results: Improvement, Response rate and Remission rates at the end of eight weeks were 71.11%, 83.33% and58.33% for escitalopram and 59.35%, 34.14% and75.6% for milnacipran respectively. Adverse experiences were reported by 14% of patients in escitalopram group and 79.2% patients in milnacipran group at 8 weeks. Additionally, there were significantly lesser dropouts due to adverse events in escitalopram (3.70%) than in milnacipran group (30%).Conclusions: Escitalopram, the Senantiomer of citalopram, is a safe and effective antidepressant with potentially superior tolerability and comparable efficacy to the dual reuptake inhibitor, Milnacipran.

scholarly journals New classes of antidepressant drugs

1999 ◽  
Vol 5 (2) ◽  
pp. 104-111 ◽  
Author(s):  
Allan I. F. Scott
Keyword(s):  
Reuptake Inhibitor ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Tricyclic Antidepressants ◽  
Antidepressant Drug ◽  
Antidepressant Drugs ◽  
Noradrenaline Reuptake ◽  
Meta Analyses ◽  
Prevention Of Relapse ◽  
Serotonergic Antidepressant ◽  
Noradrenaline Reuptake Inhibitor

The January 1997 issue of this journal contained four reviews that compared tricyclic antidepressants with selective serotonin reuptake inhibitors (SSRIs) and other newer antidepressants in terms of their pharmacology (Palazidou, 1997), adverse effects, potential drug interactions and toxicity (Henry, 1997), efficacy in the prevention of relapse and recurrence (Edwards, 1997), and findings from meta-analyses (Anderson, 1997). In July 1997 reboxetine was promoted as the first selective noradrenaline reuptake inhibitor (NARI), and in October of the same year mirtazapine was promoted as the first noradrenergic and specific serotonergic antidepressant (NaSSA). Milnacipran is presently being registered by the manufacturers, after which it will be the second antidepressant drug promoted as a specific serotonin and noradrenaline reuptake inhibitor (SNRI).

scholarly journals Treatment Patterns and Sequences of Pharmacotherapy for Patients Diagnosed with Depression in the United States: 2014 through 2019

2019 ◽  
Author(s):  
David M. Kern ◽  
M. Soledad Cepeda ◽  
Frank Defalco ◽  
Mila Etropolski
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Tricyclic Antidepressants ◽  
Antidepressant Medication ◽  
The United States ◽  
Treatment Patterns ◽  
Inpatient Hospitalization ◽  
Class Level ◽  
Treatment Of Depression ◽  
Antidepressive Treatment

Abstract Background : Understanding how patients are treated in the real-world is vital to identifying potential gaps in care. We describe the current pharmacologic treatment patterns for the treatment of depression. Methods : Patients with depression were identified from four large national claims databases during 1/1/2014-1/31/2019. Patients had ≥2 diagnoses for depression or an inpatient hospitalization with a diagnosis of depression. Patients were required to have enrollment in the database ≥1 year prior to and three years following their first depression diagnosis. Treatment patterns were captured at the class level and included selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, other antidepressants, anxiolytics, hypnotics/sedatives, and antipsychotics . Treatment patterns were captured during all available follow-up. Results : We identified 269,668 patients diagnosed with depression . The proportion not receiving any pharmacological treatment during follow-up ranged from 31% to 54%. Of the treated, approximately half received ≥2 different classes of therapy, a quarter received ≥3 classes and 10% received 4 or more. SSRIs were the most common first-line treatment; however, many patients received an anxiolytic, hypnotic/sedative, or antipsychotic prior to any antidepressive treatment. Treatment with a combination of classes was relatively uncommon across all treatment lines. Conclusions : Many patients diagnosed with depression go untreated and many others receive a non-antidepressant medication class as their first treatment. More than half of patients received more than one type of treatment class during the study follow up, suggesting that the first treatment received may not be optimal for most patients.

Alterations in Acylcarnitines, Amines, and Lipids Inform about Mechanism of Action of Citalopram/Escitalopram in Major Depression

2020 ◽  
Author(s):  
Siamak MahmoudianDehkordi ◽  
Ahmed T. Ahmed ◽  
Sudeepa Bhattacharyya ◽  
Xianlin Han ◽  
Rebecca A. Baillie ◽  
...  
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Rating Scale ◽  
Lipid Membrane ◽  
Antidepressant Medication ◽  
Methionine Sulfoxide ◽  
Therapeutic Benefit ◽  
Mechanisms Of Action ◽  
Research Network ◽  
One Carbon Metabolism ◽  
Hamilton Rating Scale

AbstractSelective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder (MDD), yet their mechanisms of action are not fully understood and their therapeutic benefit varies among individuals. We used a targeted metabolomics approach utilizing a panel of 180 metabolites to gain insights into mechanisms of action and response to citalopram/escitalopram. Plasma samples from 136 participants with MDD enrolled into the Mayo Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) were profiled at baseline and after 8 weeks of treatment. After treatment, we saw increased levels of short-chain acylcarnitines and decreased levels of medium- and long-chain acylcarnitines, suggesting an SSRI effect on β-oxidation and mitochondrial function. Amines – including arginine, proline, and methionine-sulfoxide – were upregulated while serotonin and sarcosine were downregulated, suggesting an SSRI effect on urea cycle, one-carbon metabolism and serotonin uptake. Eighteen lipids within the phosphatidylcholine (PC aa and ae) classes were upregulated. Changes in several lipid and amine levels correlated with changes in 17-item Hamilton Rating Scale for Depression scores (HRSD17). Differences in metabolic profiles at baseline and post-treatment were noted between participants who remitted (HRSD17≤7) and those who gained no meaningful benefits (<30% reduction in HRSD17). Remitters exhibited a) higher baseline levels of C3, C5, alpha-aminoadipic acid, sarcosine and serotonin; and b) higher week-8 levels of PC aa C34:1, PC aa C34:2, PC aa C36:2 and PC aa C36:4. These findings suggest that mitochondrial energetics – including acylcarnitine metabolism, transport and its link to β-oxidation – and lipid membrane remodeling may play roles in SSRI treatment response.

Panic in Australia

1998 ◽  
Vol 13 (S2) ◽  
pp. 71s-74s
Author(s):  
GD Burrows ◽  
TR Norman ◽  
SR Ellen ◽  
KP Maguire ◽  
FK Judd
Keyword(s):  
Major Depression ◽  
Panic Disorder ◽  
Monoamine Oxidase ◽  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Tricyclic Antidepressants ◽  
Serotonin Reuptake Inhibitors ◽  
Selective Serotonin ◽  
Psychiatric Conditions ◽  
To Receive

SummaryPanic disorder is widespread in Australia, often in combination with other psychiatric conditions such as agoraphobia or major depression. Pharmacotherapy for panic disorder in Australia commenced with benzodiazepines, and later progressed to tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). More recently, treatment has moved towards use of the selective serotonin reuptake inhibitors (SSRIs), which are effective and better tolerated. Paroxetine is the first drug of this class to receive approval for treatment of panic disorder in Australia.

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