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A double-blind multicenter trial comparing sertraline and fluoxetine in outpatients with major depression
Abstract
Sertraline and fluoxetine have pharmacokinetic and pharmacologic differences, which may be of clinical relevance.
A randomized, double-blind, parallel-group study of 6 weeks' duration comparing the efficacy and safety of sertraline (50-100 mg/day) with those of fluoxetine (20-40 mg/day) was conducted in 286 psychiatric outpatients with DSM-III-R major depression or bipolar disorder (depressed). Primary efficacy measurements consisted of the 17-item Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions (CGI) scale. Secondary measurements included the Hamilton Rating Scale for Anxiety (HAM-A), the Raskin Depression Scale, the Covi Anxiety Scale, and the Leeds Sleep Questionnaire. Additionally, scores for two items and five factors from the HAM-D were analyzed.
Efficacy was based on 124 evaluable patients in each treatment group. As measured by HAM-D and CGI-Severity scores, there was a significant (p < .001) improvement from baseline to each follow-up visit in both treatment groups with no statistically significant difference between groups. There was also no significant difference in the proportion of responders in each group. CGI-Improvement responder rates were 69% for sertraline and 67% for fluoxetine. Results of secondary efficacy measurements followed the same trend, although from the second week of treatment there was a numerical advantage (not statistically significant) for sertraline over fluoxetine in improving anxiety symptoms as measured by the total HAM-A score. Headache and nausea were the most frequently reported events for both drugs. The incidence of early patient withdrawals due to treatment-emergent adverse events was 14% for sertraline and 13% for fluoxetine. The starting dosage (sertraline 50 mg/day, fluoxetine 20 mg/day) was the final dosage in 76% of patients in both treatment groups.
Sertraline and fluoxetine were equally effective and well tolerated in patients with major depression and associated anxiety.
... Six studies compared fluoxetine to sertraline. 54,55,73,[75][76][77] The top-level evidence consisted of two effectiveness trials 54,55 and one efficacy trial 78 with long periods of follow-up. ...
... Three additional fair-rated trials did not find any significant differences in primary outcome measures (HAM-D, MADRS, CGI-S). 73,75,77,79 Treatment durations varied from 6 to 16 weeks. One study was conducted in 236 participants older than 60 years. ...
... 79 We conducted a meta-analysis of five of these studies comparing the effects of fluoxetine to sertraline on HAM-D scores at study endpoint. 54,73,[75][76][77] All studies except one were financially supported by the manufacturer of sertraline. Results are presented in Exhibit 4. We excluded two studies because different diagnostic scales measured the outcome. ...
... But over the years, their roles have expanded from merely providing shelter to travelers to taking care of the sick and dying people. In the 19 th century, hospices operating in countries like Ireland and France started providing terminal care at the endof-life stage (Bennahum, 2003). However, it was only in 1967 that the term hospice was first applied to this specialized care that was being provided to the dying patients. ...
... The work done by this hospice was soon recognized and appreciated by health care providers throughout the world. (Bennahum, 2003;Meghani, 2004). In 1977, the National Hospice Organization (NHO), was established in the U.S., which included all those institutions that offered such services. ...
... The choice of antidepressant was restricted to the two-second generation molecules available at the hospital, especially that Sertraline and Fluoxetine belong to the same class of SSRI. However, apart from the serotonin transporter inhibition, Fluoxetine and Sertraline do not have the same mechanisms of action (78). Larger studies could allow the generalization of these results. ...
Introduction:
In spite of several approaches and therapeutic measures, treatment-resistant depression (TRD) continues to inflict serious, individual and collective consequences. Therefore, there is a persistent need to scrutinize the concept of TRD in order to adapt the therapeutic strategies.
Aim:
To estimate the incidence of TRD in patients with a first major depressive episode (MDD), and study factors associated with resistance.
Methods:
A descriptive prospective longitudinal study of outpatients with a first MDD, was conducted. Patients with a history of subthreshold hypomania were excluded. Eligible patients were put on a selective serotonin reuptake inhibitor (SSRI), either fluoxetine or sertraline. Participants were followed regularly until they had a therapeutic response or they met the criteria for TRD.
Results:
The study involved 82 adults. The incidence of treatment-resistant depression was 19.4% CI95%=[5.5-33.3]. Among the sociodemographic and clinical factors, family history of psychosis (p=0.038) and chronic respiratory comorbidities (p=0.016) were associated with TRD. The small size of the sample is a potential limitation of this study. Besides, the use of only two SSRIs could influence the results.
Conclusion:
In this study, the incidence of TRD was at the lower limit of the rates reported in clinical studies. Clinical factors associated with TRD suggest the relevance of genotype analysis to identify patients with TRD. Furthermore, our results highlight the importance of heeding comorbidities to optimize care. Larger multicenter studies are needed to generalize.
... Safety and tolerability of antidepressant co-treatment in acute major depressive disorder: results from a systematic review and exploratory meta-analysis 1. Introduction For major depressive disorder (MDD), clinical guidelines suggest as first-line treatment evidence-based, depression-focused psychotherapy with or without monotherapy of an antidepressant (AD) [1][2][3]. Response rates to initial AD monotherapy range between 50 and 75%, whereas remission rates are around 30% [4][5][6][7][8][9]. For patients not responding to the initial treatment, optimization of the AD dose, a switch to another AD, augmentation with various non-ADs agents with antidepressant efficacy, or the co-treatment with two ADs are recommended [1][2][3]. ...
... Available data suggest there are critical differences in drug pharmacodynamics besides pharmacokinetic diversities in this group which is responsible for the differential clinical effectiveness. Clinical observations are suggestive of significantly different responses and especially greater cognitive improvement and anxiety relief with sertraline comparing with fluoxetine [25,26], the two widely used SSRIs, in Iranian population. Fluoxetine is the least selective serotonin reuptake inhibitor with norepinephrine and dopamine reuptake inhibition as well whereas sertraline is the second most potent inhibitor of serotonin reuptake and the second most selective blocker of serotonin over noradrenaline uptake. ...
Background
Extensive distribution of the different components of renin angiotensin system (RAS) in the brain, along with their roles in promoting anxiety, depression and brain inflammation, opposes RAS as a potential therapeutic target in major depression. Actions of angiotensin II, the main product of RAS, are reduced by antidepressants and this signifies the complex interplay of different mechanisms involved in response to therapy. Here, we hypothesized that genetic polymorphisms of RAS may affect the outcome of therapy in depressed patients.
Methods
The frequencies of variants of genes encoding for angiotensin-converting enzyme (ACE) insertion/deletion (I/D), rs4291 and rs4343 polymorphisms were determined in extracted DNAs of 200 newly diagnosed depressed patients. Patients were randomly divided into two groups, one treated with fluoxetine and the other treated with sertraline for 12 weeks. Responsive patients were determined by psychiatrist using Hamilton questionnaire and were compared with regard to their genetic variants.
Results
Carriers of the D allele and patients with DD genotype responded significantly better to sertraline than to fluoxetine (P = 0.0006, odds ratio (OR) = 3.0, 95 % confidence interval (CI) = 1.80–5.08; P = 0.006, OR = 3.7, 95 % CI = 1.66–8.29, respectively). Mutant genotypes (GG and TT) of rs4343 and rs4291 polymorphisms were also more frequent in patients responding to sertraline, though not achieving the significance level (P = 0.162 and P = 0.256, respectively).
Conclusion
These findings suggest that special genetic variants of RAS may influence or be an indicator for better response to sertraline.
... Full recognition of side effects is important in choosing an appropriate medication leading to high compliance and tolerance for patients (Higgins et al., 2010;Brambilla et al., 2005). Various studies concerning the severity and incidence of adverse events listed for the serotonin reuptake inhibitor drugs have been carried out but with different results (Fava et al., 2000;Bennie et al., 1995;Preskorn, 1995;Newhouse et al., 2000). Sexual problems can affect self-confidence, quality of life and marital and mental health. ...
Depression is among the most common psychiatric disorders in the world. Its lifetime prevalence is 25% among women. Selective serotonin reuptake inhibitors (SSRI) are common drugs used for the treatment of depression and are associated with specific complications. The purpose of this study was to evaluate the prevalence of sexual dysfunction caused by fluoxetine, citalopram and sertraline in depressed women. In this cross-sectional study, 90 women with depression treated with fluoxetine 20-40 mg (n=30), citalopram 20-40 mg (n=30) and sertraline 50-100 mg (n=30) were studied. All patients completed the A sex questionnaire to assess sexual dysfunction. The results were evaluated qualitatively and quantitatively. Sexual dysfunction was considered if a total of above 19 points, or a 5 or higher in a question or a score of 4 or higher in 3 different questions was achieved. Sexual dysfunction was observed in 53 cases (58.9%), including 18 (60%) of sertraline group, 16 patients (53.3%) of citalopram and 19 (63.3%) of fluoxetine group. Regarding this variable a significant difference was not observed between the three groups (p=0.46). In qualitative and quantitative assessment, only sexual desire was significantly lower in the sertraline group compared with citalopram group (p=0.04). Patients older than 30 years had a higher rate of sexual dysfunction compared to younger patients (p<0.001). There was no significant difference between the three drug groups concerning the incidence of sexual dysfunction. It seems that sexual function in women is not affected by SSRI drugs but age affects its incidence.
... As a result, several RCTs designed and published after the approval of escitalopram have shown that escitalopram 20 mg is particularly beneficial in severely depressed patients (baseline MADRS ]30) (7Á9), with superior effects over citalopram or paroxetine reported in this patient subgroup (baseline MADRS ]30); with the benefits improving further as baseline MADRS score gets higher (7Á9). Moreover, while escitalopram 10 mg is the optimal dose for patients with moderate depression (baseline MADRS 22Á29), its efficacy decreases in severely depressed patients (10). These results demonstrate the importance of reevaluation of a drug over time and have important consequences for HTA agencies and other decisionmakers who need to evaluate a drug at its time of launch and make a decision on whether to reimburse the drug. ...
Objective
To assess the variation of relative efficacy and tolerability of an antidepressant versus others based on both pre-marketing (registration studies) and post-marketing studies versus pre-marketing studies only in patients with major depressive disorder.
Methods
The relative efficacy and tolerability of antidepressants was assessed by mixed treatment comparisons (MTCs) using data acquired over two time periods: before registration of the reference drug escitalopram (1989–2002) and up to 5 years later (1989–2007). Ranking probability outputs were presented for efficacy, using change from baseline to 8 weeks on Montgomery–Åsberg Depression Rating Scale total score, and tolerability, using withdrawals due to adverse events.
Results
The relative efficacy and tolerability of some selected antidepressants, including escitalopram, varied considerably over the two time periods. The improved relative efficacy and tolerability of escitalopram over time, compared with citalopram, was demonstrated by greater separation of ranking probability curves for efficacy and tolerability. In 2002, escitalopram ranked low with 13.9% and 5.1% probability of being in the top four antidepressants’ relative efficacy and tolerability, respectively. In 2007, ranking probabilities for relative efficacy and tolerability of escitalopram increased to 52.5% and 82.1%, respectively.
Conclusions
Time of marketing authorization may not be the most appropriate time to evaluate the relative efficacy and tolerability of a new antidepressant based on MTC approach due to the asymmetry of information between new and older compounds. However, the first evaluation of relative effect of a new drug for health technology assessment recommendations is commonly done at this time. Re-evaluation of a drug several years after its launch is likely to provide a more accurate indication of its relative efficacy and tolerability.
... Safety and tolerability of antidepressant co-treatment in acute major depressive disorder: results from a systematic review and exploratory meta-analysis 1. Introduction For major depressive disorder (MDD), clinical guidelines suggest as first-line treatment evidence-based, depression-focused psychotherapy with or without monotherapy of an antidepressant (AD) [1][2][3]. Response rates to initial AD monotherapy range between 50 and 75%, whereas remission rates are around 30% [4][5][6][7][8][9]. For patients not responding to the initial treatment, optimization of the AD dose, a switch to another AD, augmentation with various non-ADs agents with antidepressant efficacy, or the co-treatment with two ADs are recommended [1][2][3]. ...
Introduction:
Although antidepressant (AD) monotherapy is recommended first-line for major depressive disorder (MDD), AD + AD co-treatment is common. Areas covered: We conducted the first systematic review searching PubMed/MEDLINE/PsycInfo/Embase from database inception until 1 June 2015 for acute randomized trials in ≥ 20 adults with MDD comparing AD monotherapy with AD + AD co-treatment that reported quantitative data on adverse events (AEs). Meta-analyzing 23 studies (n = 2435, duration = 6.6 weeks) AD monotherapy and AD + AD co-treatment were similar regarding intolerability-related discontinuation (risk ratio [RR] = 1.38, 95% CI = 0.89 - 1.10) and frequency of ≥ 1 AE (RR = 1.19, 95% CI = 0.95 - 1.49). Nevertheless, AD + AD co-treatment was associated with significantly greater burden regarding 4/25 AEs (tremor: RR = 1.55, 95% CI = 1.01 - 2.38; sweating: RR = 1.95, 95% CI = 1.13 -3.38, ≥ 7% weight gain: RR = 3.15, 95% CI = 1.34 - 7.41; weight gain = 2.17, 95% CI = 0.71 - 3.63 kg), but not more CNS, gastrointestinal, sexual or alertness-related AEs. However, 11/25 AEs (44.0%) were reported in only 1 - 2 studies. Adding noradrenergic and specific serotonergic antidepressants (NaSSA) or tricyclic antidepressants (TCA) to selective serotonin reuptake inhibitors (SSRIs) was specifically associated with more AEs. Expert opinion: The potential for increased AEs with AD + AD co-treatment needs to be considered vis-à-vis unclear efficacy benefits of this strategy. In particular, NaSSAs and TCAs should be added to SSRIs with caution. Clearly, more data on side-effect burden of AD + AD co-treatment are needed.
... 15 Other study demonstrated that sertraline (50-100 mg) was associated with fewer reports of trouble in sleep initiation than fluoxetine (20-40 mg), but with poorer perceptions on waking. 16 Similarly, sertraline in our study comprises 28.98% of all prescribed drugs, 35% of these shows ADRs related to sleep disturbances among these 35% all complaints of insomnia while about 1/4th of them also complaints of daytime sleeping with insomnia. A previous study found that citalopram (20-80 mg) was associated with significant improvements in HAMD sleep scores, relative to placebo although daytime sleepiness was a significantly greater problem for those taking citalopram than for placebo. ...
Background: Prescription of antidepressants has been increased from the last decade
and responsible for producing sleep disorders as adverse drug reactions (ADRs). Sleep
disorders can be divided into 3 large groups: (1) insomnia, (2) primary complaint of
daytime sleepiness, and (3) Association of disruptive behaviours during sleep, the
disorders of arousal. So active surveillance is needed to access these ADRs.
Aims and Objective: To analyze the sleep disturbances as ADRs of various
antidepressants prescribed to the patients attending psychiatry outpatient department
(OPD).
Methods: This prospective study was conducted on patients aged ≤74 years attending
Department of Psychiatry OPD and were prescribed Antidepressants for the duration
of 8 months (December, 2013-July, 2014). The ADRs reported were confirmed by
WHO UMC Causality Assessment Scale.
Results: Total number of patients enrolled on the basis of inclusion and exclusion
criteria (n=50). Total number of ADRs related to drugs prescribed were found to be
n=69. Total number of patients with sleep disturbances as ADRs were found to be
n=28.
Conclusion: The drug, most frequently implicated to cause sleep disturbances, was
mirtazapine. Increased sleep was the most common ADR, found to occur. Unusual
ADRs such as sleep talking was also seen.
... He did not mention that in the same study the mean daily dose of fluoxetine was 28 mg, which is a 40% increase from the starting dose of 20 mg. Bennie et al. 7 (Pfizer sponsored) compared fluoxetine and sertraline for the treatment of major depression with starting doses of 20 mg and 50 mg daily, respectively. Twenty-four percent of those taking sertraline had the dose doubled to 100 mg-exactly the same percentage of patients taking fluoxetine had the dose doubled to 40 mg daily. ...
... He did not mention that in the same study the mean daily dose of fluoxetine was 28 mg, which is a 40% increase from the starting dose of 20 mg. Bennie et al. 7 (Pfizer sponsored) compared fluoxetine and sertraline for the treatment of major depression with starting doses of 20 mg and 50 mg daily, respectively. Twenty-four percent of those taking sertraline had the dose doubled to 100 mg-exactly the same percentage of patients taking fluoxetine had the dose doubled to 40 mg daily. ...
... As predicted, both groups showed significant reductions in depressive symptom ratings over time, albeit the MED-only group did not show significant changes on self-rated depression scores. Approximately 50%-70% of depressed patients can be expected to demonstrate a response to an adequate trial of antidepressant medication, 60 and the rate of MED-only participants in this study who were in remission at posttreatment, by interview-rated depression criteria (50%), essentially corresponded with this. When comparing remission rates between MED-only and MED???DBT, the number of patients in remission at post-treatment was similar using the BDI. ...
... To ensure prominence of anxiety symptoms over depression symptoms, patients were required to have a Covi Anxiety Scale [19] score ≥ 9 and a Raskin Depression Scale [20] score ≤ 7. These psychiatric rating scales have long been used in clinical trials and have been shown to be valid tools for differentiating anxious and depressed patient subgroups [21,22]. Subjects were excluded from study participation if they had significant suicidal risk, had failed treatment with lorazepam or paroxetine in the past, required daily benzodiazepine use in the three months prior to study participation, or if they had most other concurrent DSM-IV mental disorders, including major depressive disorder, panic disorder with or without agoraphobia, acute stress disorder, obsessive compulsive disorder, dissociative disorder, posttraumatic stress disorder, social anxiety disorder, anorexia, bulimia, caffeine-induced anxiety disorder, alcohol or substance abuse or dependence, premenstrual dysphoric disorder, or antisocial or borderline personality disorder. ...
Fast-acting medications for the management of anxiety are important to patients and society. Measuring early onset, however, requires a sensitive and clinically responsive tool. This study evaluates the psychometric properties of a patient-reported Global Anxiety-Visual Analog Scale (GA-VAS).
Data from a double-blind, randomized, placebo-controlled study of lorazepam and paroxetine in patients with Generalized Anxiety Disorder were analyzed to assess the reliability, validity, responsiveness, and utility of the GA-VAS. The GA-VAS was completed at clinic visits and at home during the first week of treatment. Targeted psychometric analyses--test-retest reliabilities, validity correlations, responsiveness statistics, and minimum important differences--were conducted.
The GA-VAS correlates well with other anxiety measures, at Week 4, r=0.60 (p<0.0001) with the Hamilton Rating Scale for Anxiety and r=0.74 (p<0.0001) with the Hospital Anxiety and Depression Scale-Anxiety subscale. In terms of convergent and divergent validity, the GA-VAS correlated -0.54 (p<0.0001), -0.48 (p<0.0001), and -0.68 (p<0.0001) with the SF-36 Emotional Role, Social Function, and Mental Health subscales, respectively, but correlated much lower with the SF-36 physical functioning subscales. Preliminary minimum important difference estimates cluster between 10 and 15 mm.
The GA-VAS is capable of validly and effectively capturing a reduction in anxiety as quickly as 24 hours post-dose.
... Numerous clinical trials have assessed the effi cacy of antidepressants, generally indicating that antidepressant treatment of major depression is superior to placebo treatment (Dunbar et al 1993; Ellingrod and Perry 1995; Ballenger 1996; Croft et al 1999; Feighner and Overo 1999; Gorman 1999 ). The majority of studies that compare multiple antidepressants including SSRIs and tricyclic antidepressants (TCAs) show no signifi cant effi cacy differences between them (Holliday and Plosker 1993; Bennie et al 1995; Patris et al 1996; Sechter et al 1999; Stahl 2000; Kroenke et al 2001), but with very high sample size or with meta-analysis using data from multiple studies, TCAs and dual reuptake inhibitors show greater effi cacy than SSRIs (Thase 2002). The core difference between the TCAs and SSRIs lies in safety profi les and tolerability. ...
Since depression impacts all body systems, antidepressant treatments should relieve both the emotional and physical symptoms of depression. Duloxetine demonstrated antidepressant efficacy at a dose of 60 mg qd in two placebo-controlled, randomized, double-blind studies and significantly improved remission rates compared with placebo. Duloxetine-treated patients had significant reduction in severity of the symptoms of depression as assessed by the HAM-D(17), anxious symptoms as measured by the HAM-A and quality of life measures compared to placebo. Duloxetine also improved somatic symptoms, particularly painful symptoms which may have contributed to significantly improved remission rates compared to placebo. Approximately 10% of the 1139 patients with major depressive disorder in placebo-controlled trials discontinued treatment due to an adverse event, compared to 4% of the 777 patients receiving placebo. In addition to nausea (1.4% incidence), which was the most common reason for discontinuation, dizziness, somnolence, and fatigue were the most common AEs reported as reasons for discontinuation and all were considered drug-related. Duloxetine treatment lacks effects on ECG, increases heart rate, and has little effect on blood pressure or weight.
Resumen
La depresión se asocia con morbilidad y mortalidad considerables. Como los trastornos depresivos entrañan un alto riesgo de recaída, las estrategias de tratamiento incluyen el uso de un periodo de continuación de 6 meses después de la resolución del episodio agudo. La tolerabilidad es de importancia fundamental al determinar el cumplimiento y la evolución durante la terapia a largo plazo. Debido al perfil de tolerabilidad superior de los inhibidores selectivos de la recaptación de serotonina (SSRI) sobre los antiguos antidepresivos tricíclicos (TCA), aquéllos pueden ser más convenientes para una terapia prolongada. Los estudios comparativos no han mostrado diferencias entre los SSRI desde el punto de vista de la eficacia, pero los perfiles de efectos secundarios pueden variar. Se llevó a cabo un estudio comparativo doble ciego multicéntrico de sertralina y fluoxetina en pacientes ambulatorios que cumplían los criterios del DSM-III-R para trastorno depresivo mayor. Se distribuyó al azar a los pacientes para recibir sertralina (50-150 mg, n = 118) o fluoxetina (20-60 mg, n = 120) durante 24 semanas. Se hicieron evaluaciones para la depresión (HAM-D, HAD, CGI-I, CGI-S), la ansiedad (Covi), el sueño (Escala de evaluación del sueño de Leeds) y la calidad de vida (SIP) en la inclusión del estudio y en las semanas 2, 4, 8, 12, 18 y 24. Se registraron todos los acontecimientos adversos para permitir la evaluación de la tolerabilidad. En total, 88 pacientes en el grupo de sertralina completaron el estudio en comparación con 79 en el grupo de fluoxetina. Los efectos secundarios fueron responsables de la supresión prematura del tratamiento de siete pacientes con sertralina (6%) y 12 (10%) pacientes con fluoxetina. Se incluyó a 234 pacientes en un análisis de intención de tratamiento (ITT) hasta la última visita (116 pacientes con sertralina, 118 con fluoxetina). Al final del estudio, ambos tratamientos produjeron una mejoría significativa sobre la línea de base en todas las variables de eficacia ( P < 0,001). Aunque la magnitud de los cambios globales en la depresión, la ansiedad y la calidad de vida fue más grande con sertralina que con fluoxetina, ninguna de las diferencias entre grupos alcanzó significación estadística. Sin embargo, se observaron diferencias significativas en favor de la sertralina para elementos individuales de la HAM-D, incluidos el elemento 4 (insomnio precoz, P = 0,04), el elemento 9 (agitación, P = 0,02) y el elemento 13 (síntomas somáticos generales, P = 0,008). Además, la sertralina se asoció con un rendimiento significativamente superior en la Escala de Evaluación del Sueño de Leeds y en los elementos de la SIP relacionados con el sueño y el descanso, el comportamiento emocional y no estar encamado. Tanto la sertralina como la fluoxetina se toleraron bien, sin diferencias significativas entre los tratamientos.
INTRODUCCION Los trastornos depresivos son una causa frecuente de consulta en todos los niveles asistenciales. Los antidepresivos tricíclicos (ATC) han constituído la base del tratamiento farmacológico de la depresión durante más de cuatro décadas, siendo habitual que los trastornos depresivos se diagnosticaran por debajo de su prevalencia, y que, con frecuencia, los casos diagnosticados fueran tratados insuficientemente. 1 En los últimos años ha aparecido una nueva generación de antidepresivos, los inhibidores selectivos de la recaptación de serotonina (ISRS). Los datos disponibles sugieren una eficacia equivalente para los medicamentos antidepresivos entre y dentro de una misma clase. La elección de un antidepresivo en la práctica entonces se debe realizar teniendo en cuenta las características de cada fármaco y los requerimientos de cada paciente. En la elección de un tratamiento antidepresivo se debe considerar la historia clínica(antecedentes personales o familiares de respuesta a antidepresivos), la existencia de otras enfermedades concomitantes (como hipertensión, enfermedad cardíaca, glaucoma, uropatía obstructiva, demencia, epilepsia), las contraindicaciones, medicación concomitante, y el costo. A medida que se han acumulado datos sobre el uso con estos medicamentos, se ha discutido sobre a la eficacia y efectividad comparativa de los nuevos antidepresivos frente a los clásicos, y sobre la tolerancia de sus efectos adversos. La posibilidad de establecer ventajas o desventajas relativas entre distintos antidepresivos es muy limitada durante las primeras fases de comercialización y la mayor parte de los ensayos clínicos publicados forman parte del proceso de desarrollo del fármaco, y por tanto están planteados para probar su eficacia y seguridad frente a placebo. Los ensayos clínicos comparativos entre los clásicos y los nuevos antidepresivos son muy pocos, y con frecuencia presentan serios errores de diseño 2-6. Diversos metaanálisis publicados y revisiones concluyen que la eficacia global de las distintas clases de antidepresivos es similar tanto en el tratamiento de los episodios agudos, como en el tratamiento de mantenimiento. 7, 8 , 9. Inhibidores Selectivos de la Recaptación de Serotonina Los ISRS son la alternativa a utilizar cuando el paciente no tolera los efectos sedantes y anticolinérgicos de los Antidepresivos Triciclicos (ATC), o cuando presenta una enfermedad
Die Hauptgruppe der serotonin-selektiven Antidepressiva stellen die serotonin-selektiven Rückaufnahme-Inhibitoren (Wiederaufnahmehemmer) (SSRI)dar. In deutschsprachigen Ländern derzeit verfügbare Substanzen sind>
Citalopram/Escitalopram
Fluoxetin
Fluvoxamin
Paroxetin
Sertralin
Some authors regard gambling as addiction. Detailed psychiatric examination revealed obsessive-compulsive syndrome in patient. The author treated the patient systematically with individual psychotherapy and sertraline from low doses up to the maximal dose (i.e. about 200 mg daily). A complete remission of the obsessive-compulsive syndrome was achieved. A number of indirect proofs demonstrate a significant role of sertraline in the aetiology of obsessive-compulsive syndrome. The most important evidence is the effectiveness of the drugs from the group of selective inhibitors of serotonin central reuptake (SI-5HT) in the treatment of obsessive-compulsive syndrome. Sertraline is safe and effective in the treatment of obsessive-compulsive syndrome. Very numerous authors have used sertraline in the treatment of this syndrome with evidently good effect. Drug doses ranged from 50 to 200 mg daily.
Objective: To assess, in depressed patients, the clinical benefit of mianserin augmentation of fluoxetine or the the benefit of switching treatment from fluoxetine to mianserin.
Method: In a 6‐week double‐blind study we compared the therapeutic efficiency and tolerance of mianserin 60 mg/day ( N =34), mianserin 60 mg/day plus fluoxetine 20 mg/day ( N =32) and continuing fluoxetine 20 mg/day ( N =38) in patients with major depression who did not respond to previous fluoxetine treatment.
Results: Intent‐to‐treat analysis showed that at week 6 the decrease in the Hamilton Depression rating scale score was significantly ( P 0.03) greater in the mianserin plus fluoxetine group when compared to the fluoxetine group (effect size 0.665). Switching from fluoxetine to mianserin gave intermediate results. Mianserin augmentation of fluoxetine was well tolerated.
Conclusion: Mianserin augmentation of fluoxetine in patients non‐responders to fluoxetine 20 mg/day increases response to treatment and is well tolerated.
Antidepressants, in general, affect sleep. The most consistent effect is suppression of the rapid eye movement (REM) sleep, and this is observed both in healthy volunteers and depressed patients. REM is affected most by drugs that block the reuptake of serotonin, like the selective serotonin-reuptake inhibitors (SSRIs) and the serotonin-noradrenaline-reuptake inhibitors (SNRIs). Further, these drugs often disrupt sleep continuity. The 5-HT1A agonist anxiolytics (azapirones) like buspirone show an REM suppressant effect but they do not affect sleep continuity. We discuss this difference in terms of likely explanatory 5-HT mechanisms for the above effects. With chronic treatment, there is gradual diminution of the sleep effects of the SSRIs. Finally, we discuss the subjective sleep effects of these drugs, which are often different from the polysomnographic ones.
The involvement of the 5-HT1A and the 5-HT1B receptor in the regulation of sleep and waking is complex due to a multitude of presynaptic and/or postsynaptic actions also involving other neurotransmitter systems. Both receptors produce an important inhibitory feed back to the serotonergic raphe neurons. Overall, most studies support the possibility that stimulation of postsynaptic 5-HT1A receptors, e.g., via systemic administration of a high dose of agonists increases wakefulness and decreases sleep. Local administration of agonists in dorsal raphe nucleus mainly produces a response similar to the “low-dose” systemic administration, decreasing wakefulness and increasing rapid eye movement (REM) sleep via disinhibition of mesopontine REM sleep promoting neurons. Systemic administration of 5-HT1B receptors agonists consistently increases wakefulness and decreases REM sleep, as do the 5-HT1A agonists. The mechanism by which 5-HT1B receptors affect state modulation remain elusive. The general arousing effects of 5-HT1A and 5-HT1B agonists should also be considered in relation to the multiple, largely redundant, neurotransmitter systems that maintain arousal. Finally, 5-HT1A and 5-HT1B receptor are important modulators of the circadian rhythm largely by affecting the response of the suprachiasmatic nucleus to light and the secretion of melatonin from the pineal gland. The development of more selective ligands seems crucial to further explore the role of these receptors in state modulation.
RESUMEN Algunos autores consideran que el juego puede ser adictivo y la observación psiquiátrica puede evidenciar un síndrome obsesivo compulsivo. El autor trato a este paciente con sertraline y psicoterapia obteniendo una remisión total. Consideramos que el setraline a dósis de 50 a 200 mg diarios es una droga adecuada para el tratamiento de estos desordenes. Palabras clave: juego, adicción, síndrome obsesivo compulsivo, sertaline. ABSTRACT Some authors regard gambling as addiction. Detailed psychiatric examination revealed obsessive-compulsive syndrome in patient. The author treated the patient systematically with individual psychotherapy and sertraline from low doses up to the maximal dose (i.e. about 200 mg daily). A complete remission of the obsessive-compulsive syndrome was achieved. A number of indirect proofs demonstrate a significant role of sertraline in the aetiology of obsessive-compulsive syndrome. The most important evidence is the effectiveness of the drugs from the group of selective Recibido: 22 febrero 2008. Aceptado: 25 marzo 2008.
Detailed psychiatric examination in my patient demonstrated evident endogenous depressive syndrome and schizoid personality. Besides that, the author, aftermultiple examinations and numerous visits, diagnosed a beginning schizophrenic process. Key words: depression-mask schizophrenic process, impulsive aggression and irritability, sertraline, perphenazine. SÍNDROME DEPRESIVO QUE ENMASCARA UN PROCESO DE ESQUIZOFRENIA QUE PRINCIPIA. EXPERIENCIA PROPIA RESUMEN La exploración psiquiátrica en el paciente mostró un proceso depresivo y una personalidad esquizoide y después de varios exámenes se diagnóstico en proceso esquizofrenico. Plabras clave: depresión que enmascara un proceso esquizofrenico, agresión e irritabilidad, sertalina, perfenazina, agresión e irritabilidad. n the environment of psychiatrists it is rather commonly known that an episode of major depression can, quite not infrequently, be the mask of beginning schizophrenic process. It is known that the highest risk of developing schizophrenia is in the 18 -25 years age group. If a patient from this age group comes to a psychiatrist with a typical episode of major depression, it should be always taken into Recibido: 9 junio 2008. Aceptado: 17 julio 2008.
Major depressive disorder (MDD) has detrimental effects on an individual's personal life, leads to increased risk of comorbidities, and places an enormous economic burden on society. Several 'second-generation' antidepressants are available as both immediate-release (IR) and extended-release formulations. The advantage of extended-release formulations may be the potentially improved adherence and a lower risk of adverse events.
We conducted a systematic review to assess the comparative efficacy, risk of harms, and patients' adherence of IR and extended-release antidepressants for the treatment of MDD.
English-language abstracts were retrieved from PubMed, EMBASE, the Cochrane Library, PsycINFO, and International Pharmaceutical Abstracts from 1980 to October 2012, as well as from reference lists of pertinent review articles and grey literature searches.
We included head-to-head randomized controlled trials (RCTs) of at least 6 weeks' duration that compared an IR formulation with an extended-release formulation of the same antidepressant in adult patients with MDD. We also included placebo-controlled trials to conduct a network meta-analysis. To assess harms and adherence, in addition to RCTs, we searched for observational studies with ≥1,000 participants and a follow-up of ≥12 weeks.
We dually reviewed abstracts and full texts and assessed quality ratings. Lacking head-to-head evidence for many comparisons of interest, we conducted network meta-analyses using Bayesian methods. Our outcome measure of choice was response on the Hamilton Depression Rating Scale.
We located seven head-to-head trials and 94 placebo- and active-controlled trials for network meta-analysis. Overall, our analyses indicate that IR and extended-release formulations do not differ substantially with respect to efficacy and risk of harms. The evidence is mixed with respect to differences in adherence, indicating lower adherence for IR formulations.
The lack of head-to-head comparisons for many drugs compromises our conclusions. Network meta-analyses have methodological limitations that need to be taken into consideration when interpreting findings.
Available evidence currently shows no clear differences between the two formulations and therefore we cannot recommend a first choice. However, if adherence or compliance with one medication is an issue, then clinicians and patients should consider the alternative medication. If adherence or costs are a problem with one formulation, consideration of the other formulation to provide an adequate treatment trial is reasonable.
Depression is common in primary care and is associated with marked personal, social and economic morbidity, thus creating significant demands on service providers. The antidepressant fluoxetine has been studied in many randomised controlled trials (RCTs) in comparison with other conventional and unconventional antidepressants. However, these studies have produced conflicting findings.Other systematic reviews have considered selective serotonin reuptake inhibitor (SSRIs) as a group which limits the applicability of the indings for fluoxetine alone. Therefore, this review intends to provide specific and clinically useful information regarding the effects of fluoxetine for depression compared with tricyclics (TCAs), SSRIs, serotonin-noradrenaline reuptake inhibitors (SNRIs), monoamineoxidase inhibitors (MAOIs) and newer agents, and other conventional and unconventional agents.
To assess the effects of fluoxetine in comparison with all other antidepressive agents for depression in adult individuals with unipolar major depressive disorder.
We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Review Group Controlled Trials Register (CCDANCTR)to 11May 2012. This register includes relevant RCTs from the Cochrane Central Register of Controlled Trials (CENTRAL) (all years),MEDLINE (1950 to date), EMBASE (1974 to date) and PsycINFO (1967 to date). No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were handsearched. The pharmaceutical company marketing fluoxetine and experts in this field were contacted for supplemental data.
All RCTs comparing fluoxetine with any other AD (including non-conventional agents such as hypericum) for patients with unipolar major depressive disorder (regardless of the diagnostic criteria used) were included. For trials that had a cross-over design only results from the first randomisation period were considered.
Data were independently extracted by two review authors using a standard form. Responders to treatment were calculated on an intention-to-treat basis: dropouts were always included in this analysis. When data on dropouts were carried forward and included in the efficacy evaluation, they were analysed according to the primary studies; when dropouts were excluded from any assessment in the primary studies, they were considered as treatment failures. Scores from continuous outcomes were analysed by including patients with a final assessment or with the last observation carried forward. Tolerability data were analysed by calculating the proportion of patients who failed to complete the study due to any causes and due to side effects or inefficacy. For dichotomous data, odds ratios (ORs) were calculated with 95% confidence intervals (CI) using the random-effects model. Continuous data were analysed using standardised mean differences (SMD) with 95% CI.
A total of 171 studies were included in the analysis (24,868 participants). The included studies were undertaken between 1984 and 2012. Studies had homogenous characteristics in terms of design, intervention and outcome measures. The assessment of quality with the risk of bias tool revealed that the great majority of them failed to report methodological details, like the method of random sequence generation, the allocation concealment and blinding. Moreover, most of the included studies were sponsored by drug companies, so the potential for overestimation of treatment effect due to sponsorship bias should be considered in interpreting the results. Fluoxetine was as effective as the TCAs when considered as a group both on a dichotomous outcome (reduction of at least 50% on the Hamilton Depression Scale) (OR 0.97, 95% CI 0.77 to 1.22, 24 RCTs, 2124 participants) and a continuous outcome (mean scores at the end of the trial or change score on depression measures) (SMD 0.03, 95% CI -0.07 to 0.14, 50 RCTs, 3393 participants). On a dichotomousoutcome, fluoxetine was less effective than dothiepin or dosulepin (OR 2.13, 95% CI 1.08 to 4.20; number needed to treat (NNT) =6, 95% CI 3 to 50, 2 RCTs, 144 participants), sertraline (OR 1.37, 95% CI 1.08 to 1.74; NNT = 13, 95% CI 7 to 58, 6 RCTs, 1188 participants), mirtazapine (OR 1.46, 95% CI 1.04 to 2.04; NNT = 12, 95% CI 6 to 134, 4 RCTs, 600 participants) and venlafaxine(OR 1.29, 95% CI 1.10 to 1.51; NNT = 11, 95% CI 8 to 16, 12 RCTs, 3387 participants). On a continuous outcome, fluoxetine was more effective than ABT-200 (SMD -1.85, 95% CI -2.25 to -1.45, 1 RCT, 141 participants) and milnacipran (SMD -0.36, 95% CI-0.63 to -0.08, 2 RCTs, 213 participants); conversely, it was less effective than venlafaxine (SMD 0.10, 95% CI 0 to 0.19, 13 RCTs,3097 participants). Fluoxetine was better tolerated than TCAs considered as a group (total dropout OR 0.79, 95% CI 0.65 to 0.96;NNT = 20, 95% CI 13 to 48, 49 RCTs, 4194 participants) and was better tolerated in comparison with individual ADs, in particular amitriptyline (total dropout OR 0.62, 95% CI 0.46 to 0.85; NNT = 13, 95% CI 8 to 39, 18 RCTs, 1089 participants), and among the newer ADs ABT-200 (total dropout OR 0.18, 95% CI 0.08 to 0.39; NNT = 3, 95% CI 2 to 5, 1 RCT, 144 participants), pramipexole(total dropout OR 0.12, 95% CI 0.03 to 0.42, NNT = 3, 95% CI 2 to 5, 1 RCT, 105 participants), and reboxetine (total dropout OR0.60, 95% CI 0.44 to 0.82, NNT = 9, 95% CI 6 to 24, 4 RCTs, 764 participants).
The present study detected differences in terms of efficacy and tolerability between fluoxetine and certain ADs, but the clinical meaning of these differences is uncertain.Moreover, the assessment of quality with the risk of bias tool showed that the great majority of included studies failed to report details on methodological procedures. Of consequence, no definitive implications can be drawn from the studies' results. The better efficacy profile of sertraline and venlafaxine (and possibly other ADs) over fluoxetine may be clinically meaningful,as already suggested by other systematic reviews. In addition to efficacy data, treatment decisions should also be based on considerations of drug toxicity, patient acceptability and cost.
Sexual dysfunction (SD) is prevalent in patients with major depressive disorder (MDD) and is also associated with second-generation antidepressants (SGADs) that are commonly used to treat the condition. Evidence indicates under-reporting of SD in efficacy studies. SD associated with antidepressant treatment is a serious side effect that may lead to early termination of treatment and worsening of quality of life.
Our objective was to systematically assess the harms of SD associated with SGADs in adult patients with MDD by drug type.
We retrieved English-language abstracts from PubMed, EMBASE, the Cochrane Library, PsycINFO, and International Pharmaceutical Abstracts from 1980 to October 2012 as well as from reference lists of pertinent review articles and grey literature searches. Two independent reviewers identified randomized controlled trials (RCTs) of at least 6 weeks' duration and observational studies with at least 1,000 participants.
Reviewers abstracted data on study design, conduct, participants, interventions, outcomes and method of SD ascertainment, and rated risk of bias. A senior reviewer checked and confirmed extracted data and risk-of-bias ratings.
Random effects network meta-analysis using Bayesian methods for data from head-to-head trials and placebo-controlled comparisons; descriptive analyses calculating weighted mean rates from individual trials and observational studies.
Data from 63 studies of low and moderate risk of bias (58 RCTs, five observational studies) with more than 26,000 patients treated with SGADs were included. Based on network meta-analyses of 66 pairwise comparisons from 37 RCTs, most comparisons showed a similar risk of SD among included SGADs. However, credible intervals were wide and included differences that would be considered clinically relevant. We observed three main patterns: bupropion had a statistically significantly lower risk of SD than some other SGADs, and both escitalopram and paroxetine showed a statistically significantly higher risk of SD than some other SGADs. We found reporting of harms related to SD inconsistent and insufficient in some trials.
Most trials were conducted in highly selected populations. Search was restricted to English-language only.
Because of the indirect nature of the comparisons, the often wide credible intervals, and the high variation in magnitude of outcome, we rated the overall strength of evidence with respect to our findings as low. The current degree of evidence does not allow a precise estimate of comparative risk of SD associated with a specific antidepressant. In the absence of such evidence, clinicians need to be aware of SD as a common adverse event and should discuss patients' preferences before initiating antidepressant therapy.
Synopsis Depression is a common condition that is often unrecognised, misdiagnosed and/or undertreated. It is associated with substantial direct, indirect and intangible costs. The indirect costs of lost earnings/productility and premature death account for the majority of these costs; drug costs account for only about 1 to 2% of total costs and about 10 to 12% of direct costs. Thus, better recognition and appropriate treatment of depression would increase the direct costs associated with this illness, but would also have the potential to greatly reduce indirect costs and consequently the overall cost of depression. Because of their higher acquisition costs relative to tricyclic antidepressants (TCAs), there has been much debate about whether the use of sertraline or other selective serotonin reuptake inhibitors (SSRls) for first-line treatment of depression can be justified. While these agents have similar efficacy to TCAs, they are better tolerated and have a lower risk of death on overdosage. Despite the large economic burden of depression on society, pharmacoeconomic data on sertraline and antidepressant drugs in general are scarce. Most of the available studies on sertraline are limited to considerations of direct costs and do not assess costs from a societal perspective. In addition, a number of studies have significant methodological problems which limit determination of meaningful conclusions. Nonetheless, datafrom 2 more recent studies with fewer methodological problems than earlier studies indicated that sertraline was more cost-effective than TCAs because of fewer psychiatrist consultations, and less costly than fluoxetine because of fewer absences from work and fewer medical consultations. The cost-utility ratio of maintenance therapy of depression with sertraline appears to fall within the range of accepted cost-utility ratios of common healthcare interventions. Thus, studies to date have generally shown that overall treatment costs with sertraline and other SSRIs are no greater than those for TCAs: this is despite the lower acquisition costs of the latter agents. Therefore, it is clear from these data that it is misleading to classify antidepressant agents as expensive or inexpensive based solely on their acquisition costs. Sertraline, therefore, can be considered as a first-line alternative to TCAs and other SSRIs for the treatment of depression on both clinical and pharmacoeconomic grounds.
L’efficacité et la sécurité d’emploi de la fluoxétine, chef de file des inhibiteurs sélectifs de la recapture de la sérotonine (IRS), sont aujourd’hui bien établies dans le cadre du traitement de l’Épisode dépressif majeur caractérisé (EDM). En particulier, la mise à disposition de la fluoxétine, au même titre que les autres IRS, a permis de proposer une alternative aux antidépresseurs tricycliques dont les limitations principales sont représentées par les problèmes de tolérance. Cette avancée thérapeutique a largement contribué à changer les modalités de prise en charge de l’EDM en termes de santé publique. Les caractéristiques pharmacocinétiques et pharmacodynamiques de la fluoxétine sont bien identifiées. Cependant, en dépit des connaissances concernant la facilitation de la transmission sérotoninergique, le mécanisme d’action par lequel la fluoxétine exerce directement son activité antidépressive demeure hypothétique, au même titre que les raisons du délai d’action. Ces aspects sont discutés au vu des données les plus récentes de la littérature. Les études cliniques d’efficacité et de tolérance de la fluoxétine sont nombreuses et ont fait l’objet de plusieurs méta-analyses récentes dont nous proposons une revue critique et actualisée.
In a double-blind multicentre trial in patients with major depression, the efficacy and the tolerability of sertraline were compared to those of imipramine, during an 8-week acute treatment phase followed by a 16-week continuation treatment phase in treatment responders. A total of 104 patients who met DSM-III-R criteria for major depression, HAM-D 17-item≥18 and Raskin Depression score>Covi Anxiety score, were randomized to receive either sertraline or imipramine. The initial daily dosage of 50 mg of sertraline or imipramine was rapidly titrated upwards in increments of 50 mg/day at weekly intervals, tolerability permitting, to a maximum of 200 mg/day by the fourth week. Eighty-eight patients completed at least 3 weeks of treatment and were included in the efficacy evaluable population. Both treatment groups demonstrated similar improvements on depression and anxiety rating scales during acute treatment, however, sertraline demonstrated significantly more improvement relative to imipramine on the HAM-D and Covi Anxiety scales after 1 week of treatment. Sertraline was more effective (HAM-D 17-item, CGI-S, SCL-56 Total score, SCL-56 Depression score, Covi Anxiety score) than imipramine in reducing depressive symptoms at the end of 24 weeks of treatment. There were significant improvements in all rating scales at week 24 relative to week 8 in the sertraline group but not in the imipramine group. The SCL-56 Total score, SCL-56 Depression score, Raskin Depression score and Covi Anxiety score at week 24 relative to week 8 showed significantly greater improvement in the sertraline group compared to the imipramine group. Imipramine was associated with a significantly higher incidence of dry mouth, sweating, constipation, palpitations, and a significantly higher heart rate and blood pressure. Sertraline was associated with a significantly higher incidence of diarrhoea/loose stools and insomnia. This study demonstrated a faster onset of therapeutic effect for sertraline relative to imipramine, reflecting the initiation of sertraline in a therapeutic dose of 50 mg/day and the need for gradual titration of imipramine to a therapeutic dose, at the beginning of treatment. Although efficacy was similar in both treatment groups at the end of the 8 weeks of acute therapy, sertraline-treated patients continued to manifest gradual improvements in depressive and anxiety symptoms during the 16 weeks of continuation therapy such that sertraline-treated patients were significantly more improved at the end of 24 weeks of therapy. © 1997 John Wiley & Sons, Ltd.
Background:
Sleep disturbance is a common complaint in major depressive disorder (MDD) including impairment of both subjective and objective parameters. All antidepressants affect sleep architecture and quality.
Aim:
This trial was designed to compare the effects of short-term use of citalopram with fluoxetine on sleep quality (SQ) of patients with MDD based on Diagnostic and Statistical Manual for Mental Disorders - Text Revision 4th edition (DSM-IV-TR) criteria.
Patients and methods:
Patients who met the study criteria entered this open-label study. Sleep quality and depression severity were evaluated by using Pittsburgh Sleep Quality Index (PSQI) and Beck Depression Inventory-II (BDI-II), respectively. Patients could not have received any antidepressant for at least one month prior entering the study. Subjects were assigned to receive either fluoxetine or citalopram for 8 weeks. The relationships between SQ and severity of depression were also studied at weeks 4 and 8. Data was analyzed by using SPSS 11.5 version.
Results:
Nineteen patients received fluoxetine 20-40 mg/day and 21 received citalopram 20-40 mg/day. After 4 and 8 weeks treatment with both fluoxetine and citalopram, significant improvements in SQ were noted in both groups. However, no significant difference between the two groups was observed. Additionally, a significant and positive correlation between improvements in SQ and depression was noted after 8 weeks treatment with citalopram but not with fluoxetine.
Conclusions:
This study noted that both citalopram and fluoxetine improved SQ in outpatients with MDD after 8 weeks without any significant difference between the 2 groups.
BACKGROUND: Though encouraging evidence exists for the use of folic acid as an augmenting agent to antidepressants, evidence regarding its optimal dosage is lacking. METHODS: Forty-two female out-patients with moderate (with or without somatic syndrome) or severe depressive episodes (without psychotic symptoms) diagnosed as per ICD-10 criteria, were randomized in a double-blind fashion to receive either 20mg fluoxetine and a relatively low dose folic acid (1.5mg/day; n=23; Group I) or 20mg fluoxetine and high dose folic acid (5mg/day; n=19; Group II). Primary outcome measures were weekly changes of scores on Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI) for 6 weeks. RESULTS: Group II patients showed greater improvement in both HDRS [Mean (SD) baseline HDRS score=21 (2.3) for group I and 20.0 (1.4) for group-II; time X group interaction effect: p=0.01] and BDI [Mean (SD) baseline BDI score=25.1 (5.2) for group-1 and 23.1 (2.7) for group-II; time X group interaction effect: p=0.01]. With regard to HDRS, 7 (36.8%) group II patients remitted compared to 2 (8.7%) group I patients (p=0.03); 9 (47.4%) patients of group II responded when compared to 6 (26.1%) from group I (p=0.15). When BDI was considered, 5 (26.3%) group II patients remitted when compared to 2 (8.7%) from group I (p=0.13); 10 patients (52.6%) from group II responded when compared to 5 (21.7%) from group I (p=0.04). No adverse effects were noted in either group. LIMITATIONS: Lack of a placebo arm and small sample size. CONCLUSION: Compared to folic acid 1.5mg/day, augmentation with 5mg/day may be more beneficial in female patients with depressive episodes taking fluoxetine 20mg/day.
Investigated whether there are clinically relevant differences with the selective serotonin (5-hydroxytryptamine [5-HT]) reuptake inhibitors (SSRIs) citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline in terms of their (1) pharmacodynamic and pharmacokinetic (P&P) and (2) clinical (i.e. efficacy, tolerability, adverse events and safety) profiles in the treatment of depression. Examination of the large body of literature on the P&P of SSRIs indicated that, except for a few special situations (such as breast feeding), the many differences that the SSRIs show in their P&P profile are probably of limited importance in clinical practice. Also, the 16 head-to-head comparisons between SSRIs published before January 1997 were reviewed. Data do not reveal unequivocal, clinically relevant differences between the SSRIs in terms of general efficacy, profile of action, speed of onset of action, total severity or profile of adverse events, or safety. Thus, the differences between the SSRIs may lead the clinician when making a choice in
individual cases. However, neither P&P considerations nor direct clinical comparisons between SSRIs provide data that can assist clinicians in making a rational
general choice between these drugs. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
The disadvantages of the standard tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs), in terms of side-effects and fatal overdose, led to the development and release of seven new antidepressants in the USA in the past eight years with approximately another ten in various stages of development. This paper will focus on how recent advances in biochemistry and kinetics have led to improved efficacy. In particular, the more specific 5-HT agents appear effective for ‘typical’ depression and pain; the less specific ones for depression associated with obsessive-compulsive disorder. The selective serotonin reuptake inhibitors (SSRIs) are particularly suited for treatment of depression associated with diabetes mellitus; the serotonin and norepinephrine reuptake inhibitor (SNRI), venla-faxine, for resistant depression; and bupropion, for atypical depression. The serotonin receptor modulator (SRM), nefazodone, in contrast, is particularly suited for the treatment of depression associated with insomnia because of its combined SSRI and post-synaptic 5-HT2A/C receptor antagonist effects. In terms of kinetics, important factors include, particularly: elimination half-lives, linearity of kinetics, therapeutic blood levels, effects on hepatic microen-zymes, and effects on memory and alertness. Discussion of these seven antidepressants is followed by a brief review of knowledge concerming other potential antidepressants in development.
Concomitant prescribing of benzodiazepines during antidepressant therapy may increase patient exposure to undesirable side-effects, increase the total cost of therapy, and reflect impairment of health-related quality of life. This study examines concomitant benzodiazepine prescriptions after initiation of therapy on three commonly prescribed SSRIs: fluoxetine, paroxetine, and sertraline. A retrospective analysis of prescribing behaviours of physicians from general practices in the United Kingdom utilises a statistical model that addresses the non-negative values and skewed distribution found in count data measures of benzodiazepine prescriptions. An adjustment is made for potential sample selection bias that might result from factors correlated with both antidepressant choice and benzodiazepine prescribing. The distribution of patients receiving benzodiazepine prescriptions across drug cohorts is: 5.4% of the fluoxetine cohort; 6.4% of paroxetine patients; and 4.3% of sertraline patients. The main results show that initiation of antidepressant therapy on paroxetine is associated with receipt of an additional 0.19 benzodiazepine prescriptions in the following six month period relative to initiation on fluoxetine. However, for the average patient receiving a prescription for an anxiolytic or a sedative-hypnotic, initiation on paroxetine is associated with receipt of an additional 3.42 benzodiazepine prescriptions relative to treatment with fluoxetine. For the average patient, antidepressant therapy with sertraline was associated with 0.05 fewer benzodiazepine prescriptions relative to treatment with fluoxetine. Also, for the average patient who receives benzodiazepine prescriptions, initiation of therapy on sertraline is associated with 0.95 fewer benzodiazepine prescriptions relative to fluoxetine treatment.
In a retrospective study, we sought to determine medication dosages usually prescribed to obtain euthymia in 59 outpatients with a diagnosis of major depression treated with fluoxetine or sertraline. Charts of veterans admitted to the outpatient mental health clinic at the West Los Angeles Veterans Hospital with a diagnosis of major depression and treated with either fluoxetine or sertraline were reviewed. Progress notes were analyzed for a 6-month time period after the initiation of the medication treatment, and improvement was rated by a physician blind to the drug used for treatment. No significant differences were found in overall response rates between the fluoxetine (81% responders) and sertraline (76% responders) groups. Eighty-one percent of the fluoxetine responders compared to 32% of sertraline responders were at the manufacturer's recommended starting dose (MRSD) at the time of clinical response. One-third of patients receiving sertraline were started on or rapidly titrated to more than 50 mg/day. When only those patients receiving an adequate trial of sertraline at 50 mg were considered, 47% required a dose increase to achieve a remission. These data suggest that 50 mg of sertraline may be inadequate for some patients to achieve a resolution of symptoms of major depression and that many clinicians currently prescribe in a manner suggesting that they believe the MRSD is a suboptimal dosage. Depression and Anxiety 9:78–82, 1999. Published 1999 Wiley-Liss, Inc. This article is a US Government work, and, as such, is in the public domain of the United States of America.
In a double-blind multicentre trial in patients with major depression, the efficacy and the tolerability of sertraline were compared with those of fluoxetine, during an eight-week acute treatment phase followed by a 24-week continuation treatment phase in treatment responders.
A total of 165 patients who met DSM III-R criteria for moderate to severe major depression were randomized to receive either sertraline or fluoxetine for short-term and continuation treatment with initial daily dosages of either 50 mg of sertraline or 20 mg of fluoxetine. In the event of an inadequate response after 4 weeks of double-blind therapy these doses could be doubled.
Both treatment groups demonstrated similar improvements on both the Hamilton Rating Scale for Depression (HAM-D) and the Montgomery and Asberg Depression Rating Scale (MADRS), during the acute phase as well as during the continuation phase. Both sertraline and fluoxetine were well tolerated, the most common side-effects being gastrointestinal symptoms. Significantly more patients in the fluoxetine-treatment group experienced activationg adverse events.
The study demonstrates similar antidepressant efficacy and tolerability for sertraline and fluoxetine in acute and continuation treatment and equivalence of sertraline 50 mg daily with fluoxetine 20 mg daily in the treatment of depression.
This thesis corresponds to 20 weeks of full-time work for the author.
This paper provides an overview of the literature on depression in the elderly, and draws the attention of the readers to some, but not all, important issues related to this condition, which is still awaiting further exploration in its clinical presentation, epidemiology, treatment and prognosis. Aetiological factors are also briefly considered in the chapter.
The efficacy of depression-targeted, time-limited psychotherapies as acute phase treatments for mild-to-moderately depressed outpatients with MDD is clear. It is often equal to medication, and may be preferred in milder, uncomplicated, nonchronic cases. Problem-solving therapy (PST) or Bibliotherapy (BBT) also appear efficacious in this population. Maintenance treatments appear beneficial but are exceeded by medication. However, converting medication responders into remitters with psychotherapy seems an effective approach.
Second-generation antidepressants dominate the management of major depressive disorder (MDD), but evidence on the comparative benefits and harms of these agents is contradictory.
To compare the benefits and harms of second-generation antidepressants for treating MDD in adults.
English-language studies from PubMed, Embase, the Cochrane Library, PsycINFO, and International Pharmaceutical Abstracts from 1980 to August 2011 and reference lists of pertinent review articles and gray literature.
2 independent reviewers identified randomized trials of at least 6 weeks' duration to evaluate efficacy and observational studies with at least 1000 participants to assess harm.
Reviewers abstracted data about study design and conduct, participants, and interventions and outcomes and rated study quality. A senior reviewer checked and confirmed extracted data and quality ratings.
Meta-analyses and mixed-treatment comparisons of response to treatment and weighted mean differences were conducted on specific scales to rate depression. On the basis of 234 studies, no clinically relevant differences in efficacy or effectiveness were detected for the treatment of acute, continuation, and maintenance phases of MDD. No differences in efficacy were seen in patients with accompanying symptoms or in subgroups based on age, sex, ethnicity, or comorbid conditions. Individual drugs differed in onset of action, adverse events, and some measures of health-related quality of life.
Most trials were conducted in highly selected populations. Publication bias might affect the estimates of some comparisons. Mixed-treatment comparisons cannot conclusively exclude differences in efficacy. Evidence within subgroups was limited.
Current evidence does not warrant recommending a particular second-generation antidepressant on the basis of differences in efficacy. Differences in onset of action and adverse events may be considered when choosing a medication.
Agency for Healthcare Research and Quality.
Sertraline is a selective serotonin reuptake inhibitor that has been used and studied extensively throughout the world and found to be safe and well tolerated in numerous patient populations, including those with either psychiatric and/or medical comorbidities. Randomized clinical trials have shown that it is an effective treatment for depressive and anxiety disorders and its efficacy is unaffected by psychiatric comorbidity. In non-comorbid patients, sertraline is effective for the acute treatment of major depressive disorders and prevention of relapse or recurrence. It is effective for acute treatment and longer-term management of social anxiety disorder, posttraumatic stress disorder,panic disorder, and generalized anxiety disorder. In adults and in pediatric patients, it is an effective short-term and long-term treatment for obsessive compulsive disorder.Sertraline has a good tolerability profile and has low fatal toxicity. In summary, sertraline is as effective as other antidepressants over a wide range of indications but may offer tolerability benefits as well as efficacy in patients with psychiatric and/or medical comorbidities and certain subtypes of depression.
The National Institute for Health and Clinical Excellence clinical practice guideline on the treatment of depressive disorder recommended that selective serotonin reuptake inhibitors should be the first-line option when drug therapy is indicated for a depressive episode. Preliminary evidence suggested that sertraline might be slightly superior in terms of effectiveness.
To assess the evidence for the efficacy, acceptability and tolerability of sertraline in comparison with tricyclics (TCAs), heterocyclics, other SSRIs and newer agents in the acute-phase treatment of major depression.
MEDLINE (1966 to 2008), EMBASE (1974 to 2008), the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to July 2008. No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were hand-searched. Pharmaceutical companies and experts in this field were contacted for supplemental data.
Randomised controlled trials allocating patients with major depression to sertraline versus any other antidepressive agent.
Two review authors independently extracted data. Discrepancies were resolved with another member of the team. A double-entry procedure was employed by two reviewers. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy (the number of patients who responded or remitted), acceptability (the number of patients who failed to complete the study) and tolerability (side-effects).
A total of 59 studies, mostly of low quality, were included in the review, involving multiple treatment comparisons between sertraline and other antidepressant agents. Evidence favouring sertraline over some other antidepressants for the acute phase treatment of major depression was found, either in terms of efficacy (fluoxetine) or acceptability/tolerability (amitriptyline, imipramine, paroxetine and mirtazapine). However, some differences favouring newer antidepressants in terms of efficacy (mirtazapine) and acceptability (bupropion) were also found. In terms of individual side effects, sertraline was generally associated with a higher rate of participants experiencing diarrhoea.
This systematic review and meta-analysis highlighted a trend in favour of sertraline over other antidepressive agents both in terms of efficacy and acceptability, using 95% confidence intervals and a conservative approach, with a random effects analysis. However, the included studies did not report on all the outcomes that were pre-specified in the protocol of this review. Outcomes of clear relevance to patients and clinicians were not reported in any of the included studies.
The objective of this study was to determine the effect of industry bias in a systematically reviewed body of evidence of head-to-head trials.
We limited our analysis to published head-to-head randomized controlled trials of selective serotonin reuptake inhibitors (SSRIs) identified in a comparative effectiveness review. Two reviewers independently determined the status of funding for each trial. We classified drugs into one of two groups: (1) drugs associated with the funding source and (2) drugs not associated with the funding source. To determine the effect of any underlying industry bias, we conducted relative-benefit meta-analyses comparing the response rates of drugs when associated with the funding source with response rates of the same drugs when not associated with the funding source.
Thirteen out of 20 studies (65%) numerically favored drugs associated with the funding source over drugs used as controls. The pooled response rates of SSRIs, when associated with the funding source, are significantly greater than those of the same SSRIs when not associated with the sponsor (relative benefit=1.07; 95% confidence interval=1.02-1.11). The difference, however, is likely to be not of clinical importance.
The effect of industry bias in comparative effectiveness reviews might play a lesser role than in systematic reviews of placebo-controlled trials.
KEY MESSAGES: Efficacy and safety for the newer antidepressants in adults Background Depression is a varied illness, patients may present with symptoms such as lack of initiative, a sense of meaninglessness, depressive thoughts and/or suicidal behaviour. Problems with sleep, lack of appetite, energy, drive, anxiety and concentration are also common. Our understanding of the neurobiological causes of depression is incomplete. Reduced accessibility of monoaminerge neurotransmitters in the central nervous systems is one possible explanation. Several antidepressant drugs are available. SSRI (selective serotonin reuptake inhibitors) and other second generation anti depressants have been increasingly used in recent years. Antidepressants increase the accessibility of serotonin and/or noradrenalin, either by inhibiting the reuptake or inhibiting the decomposition. This does not seem to explain the effect. Methods We have systematically reviewed the literature for effect and safety in head-tohead studies of SSRI and other second generation antidepressants used in adults with depression. The literature was identified by a systematic search in international, electronic databases. We also received literature from the pharmaceutical industry. We assessed and summarised studies that fulfilled our predetermined criteria. Results 23 studies are included in the report. The 23 studies deal with 12 different comparisons out of 66 possible. Nine different antidepressants were compared. The documentation is of low quality for most of the comparisons. We did not find any differences in effect and safety in the head-to-head studies we analyzed with the exception of: Escitalopram was significantly more effective (response and remission rate) than citalopram. Loss to follow up was significantly lower for escitalopram than for citalopram. Citalopram had a significantly lower adverse event rate than venlafaxin. Mirtazapin was significantly more effective (remission rate) than paroxetin. Loss to follow up due to side effects was significantly lower for fluoksetin than for venlafaxin. . Conclusion We have included 12 different head-to head comparisons out of 66 possible. Nine different antidepressants were involved in the comparisons. We did not find any significant differences in effect and safety between the antidepressants except for the comparisons escitalopram versus citalopram, citalopram versus venlafaxin and mirtazapin versus paroxetin where we found significant differences for some of the outcomes. The conclusions are based on documentation of medium or low quality. Statens legemiddelverk
Conventional meta-analyses have shown inconsistent results for efficacy of second-generation antidepressants. We therefore did a multiple-treatments meta-analysis, which accounts for both direct and indirect comparisons, to assess the effects of 12 new-generation antidepressants on major depression.
We systematically reviewed 117 randomised controlled trials (25 928 participants) from 1991 up to Nov 30, 2007, which compared any of the following antidepressants at therapeutic dose range for the acute treatment of unipolar major depression in adults: bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, mirtazapine, paroxetine, reboxetine, sertraline, and venlafaxine. The main outcomes were the proportion of patients who responded to or dropped out of the allocated treatment. Analysis was done on an intention-to-treat basis.
Mirtazapine, escitalopram, venlafaxine, and sertraline were significantly more efficacious than duloxetine (odds ratios [OR] 1.39, 1.33, 1.30 and 1.27, respectively), fluoxetine (1.37, 1.32, 1.28, and 1.25, respectively), fluvoxamine (1.41, 1.35, 1.30, and 1.27, respectively), paroxetine (1.35, 1.30, 1.27, and 1.22, respectively), and reboxetine (2.03, 1.95, 1.89, and 1.85, respectively). Reboxetine was significantly less efficacious than all the other antidepressants tested. Escitalopram and sertraline showed the best profile of acceptability, leading to significantly fewer discontinuations than did duloxetine, fluvoxamine, paroxetine, reboxetine, and venlafaxine.
Clinically important differences exist between commonly prescribed antidepressants for both efficacy and acceptability in favour of escitalopram and sertraline. Sertraline might be the best choice when starting treatment for moderate to severe major depression in adults because it has the most favourable balance between benefits, acceptability, and acquisition cost.
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