Efficacy of newer medications for treating depression in primary care patients

doi:10.1016/S0002-9343(99)00316-2

The American Journal of Medicine

Volume 108, Issue 1, January 2000, Pages 54-64

https://doi.org/10.1016/S0002-9343(99)00316-2 Get rights and content

Abstract

PURPOSE: Several medications have recently been introduced for the treatment of depression. We reviewed the literature to summarize their efficacy in the treatment of depression in adult patients in primary care settings.

METHODS: We searched the literature published from 1980 to January 1998 using the Cochrane Collaboration Depression Anxiety and Neurosis Group’s specialized registry of 8,451 clinical trials, references from trials and 46 pertinent meta-analyses, and consultation with experts. We included randomized controlled trials of at least 6 weeks’ duration that measured clinical outcomes and compared one of 32 newer medications with another newer antidepressant, an older antidepressant, a placebo, or a psychosocial intervention for the treatment of depressed patients in primary care settings. The primary outcome was response rate, defined as the proportion of patients experiencing a 50% or greater improvement in depressive symptoms.

RESULTS: There were 28 randomized controlled trials involving 5,940 adult primary care patients with major depression, depression requiring treatment, dysthymia, or mixed anxiety depression. Newer agents, including selective serotonin re-uptake inhibitors, serotonin norepinephrine inhibitors, reversible inhibitors of monoamine oxidase, and dopamine antagonists, were usually compared with tricyclic agents. Average response rates were 63% for newer agents, 35% for placebo, and 60% for tricyclic agents. Newer agents were significantly more effective than placebo [risk ratio = 1.6; 95% confidence interval (CI), 1.2 to 2.1), but similar to tricyclic agents (risk ratio = 1.0; 95% CI, 0.9 to 1.1). Response rates were similar in the different types of depressive disorders, except that two small trials in frail older patients showed no significant effects of newer agents compared with placebo. Dropout rates as a result of adverse effects were 8% with newer agents and 13% with tricyclic agents (P <0.05).

CONCLUSIONS: In primary care settings, newer antidepressants are more effective than placebo and have similar efficacy compared with tricyclic agents in the acute treatment of depression. Dropout rates as a result of adverse effects are lower with newer compared with tricyclic agents. Future studies should compare the effectiveness of different therapies among primary care patients with less severe depression and greater medical and psychiatric comorbidity.

Section snippets

Methods

This work was part of a large report that identified and reviewed 315 newer pharmacotherapy and herbal treatment trials regardless of setting, which is available at www.ahcpr.gov/clinic/htm.

Results

Of the 28 trials that evaluated newer agents in 5,940 adult primary care patients 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 27 trials were conducted in Europe and one in the United States 41). Twenty trials had clearly reported funding sources 14, 16, 17, 18, 19, 20, 21, 22, 23, 27, 29, 32, 33, 34, 35, 36, 38, 40; all were sponsored by pharmaceutical companies. Clinical characteristics of participants and design

Discussion

This analysis focused on primary care trials that evaluated newer antidepressant agents, including SSRIs, norepinephrine reuptake inhibitors, reversible inhibitors of monoamine oxidase, and dopamine antagonists. Only five of the 28 trials were considered in either the US (4) or the North of England (5) guideline projects.

Our results confirmed that although antidepressant therapy is more efficacious than placebo in treating depression in primary care patients, there were no major differences in

Acknowledgements

We would like to thank Kelly Montgomery and Dave Mullins for their technical support in the development of this manuscript.

References (50)

M.E. Thase et al.
MAOIs in the contemporary treatment of depression
Neuropsychopharmacology
(1995)
D.Q.C.M. Barge Schaapveld et al.
Changes in daily life experience associated with clinical improvement in depression
J Affect Disord
(1995)
P.E. Greenberg et al.
Depressiona neglected major illness
J Clin Psychiatry
(1993)
R.D. Hays et al.
Functioning and well-being outcomes of patients with depression compared with chronic general medical illnesses
Arch Gen Psychiatry
(1995)
G. Simon et al.
Health care costs associated with depressive and anxiety disorders in primary care
Am J Psychiatry
(1995)
Depression Guideline Panel. Depression in primary care; vols. 1 and 2. Detection and diagnosis. Treatment of major...
North of England Evidence Based Guideline Development Project. The choice of antidepressants for depression in primary...
R.F. Muñoz et al.
On the AHCPR depression in primary care guidelinesfurther consideration for practitioners
Am Psychol
(1994)
L. Cooper-Patrick et al.
Characteristics of patients with major depression who received care in general medical and specialty mental health settings
Med Care
(1994)
L. Cerrahoglu et al.
The effects of antidepressive therapy in fibromyalgia syndrome
Fiz Tedavy Rehabil Derg
(1995)

C.S. Berkey et al.

A random-effects regression model for meta-analysis

Stat Med

(1995)

S. Sharp

sbe23meta-regression

Stata Tech Bull

(1998)

S. Sharp et al.

sbe16meta-analysis

Stata Tech Bull

(1997)

R. Galbraith

A note on graphical presentation of estimated odds ratios from several clinical trials

Stat Med

(1988)

Patris M, Bouchard JM, Bougerol T, et al. Citalopram versus fluoxetine: a double-blind, controlled, multicentre, phase...

Ekselius L, Von Knorring L, Eberhard G. A double-blind multicenter trial comparing sertraline and citalopram in...

Tylee A, Beaumont G, Bowden MW, Reynolds A. A double-blind, randomized, 12-week comparison study of the safety and...

S.J. Corne et al.

A double-blind comparative study of fluoxetine and dothiepin in the treatment of depression in general practice

Int Clin Psychopharmacol

(1989)

D.R. Hutchinson et al.

Paroxetine in the treatment of elderly depressed patients in general practicea double-blind comparison with amitriptyline

Int Clin Psychopharmacol

(1992)

C.A. Moon et al.

Treatment of major depression in general practicea double-blind comparison of paroxetine and lofepramine

Br J Clin Pract

(1996)

Doogan DP, Langdon CJ. A double-blind, placebo-controlled comparison of sertraline and dothiepin in the treatment of...

C.A. Moon et al.

The effects of psychomotor performance of fluvoxamine versus mianserin in depressed patients in general practice

Br J Clin Pract

(1991)

Kragh Sorensen P, Muller B, Andersen JV, Buch D, Stage KB. Moclobemide versus clomipramine in depressed patients in...

G. Beaumont et al.

A randomised, double-blind, multi-centre, parallel-group study comparing the tolerability and efficacy of moclobemide and dothiepin hydrochloride in depressed patients in general practice

Int Clin Psychopharmacol

(1993)

D. Wheatley

Minaprinean anticholinergic-free antidepressant? Results of a controlled trial of mianserin

Br J Psychiatry

(1989)

Cited by (115)

Symptom-specific effectiveness of an internet-based intervention in the treatment of mild to moderate depressive symptomatology: The potential of network estimation techniques
2019, Behaviour Research and Therapy
Citation Excerpt :
Randomized controlled trials (RCTs) provide the best evidence about the general effectiveness of treatments. They have demonstrated, for example, that pharmacological (e.g., Mulrow et al., 2000), psychotherapeutic (e.g., Churchill et al., 2001) as well as internet-based (e.g., Karyotaki et al., 2017) interventions are effective in improving overall depression severity in various groups of participants. Although these findings are highly valuable, it is important to note that measures such as overall depression severity might not do justice to the diversity of depressive symptomatology.
The internet-based intervention Deprexis® has proven to be effective in improving overall depression severity. The current pragmatic randomized controlled trial included 1013 participants with mild to moderate symptomatology and aimed to identify the symptom-specific effects of the internet-based intervention Deprexis (intervention group) in comparison to care as usual (control group). All participants -in both conditions- were permitted to use any type of treatment. Of the nine considered symptoms (assessed with the Patient Health Questionnaire), seven showed larger improvements in the intervention condition relative to care as usual (effect sizes ranging from 0.15 to 0.31). No significant differences were found for the two other symptoms. In a next step, a network was estimated including treatment condition as well as changes in all nine symptoms. The resulting network suggests that four of the seven identified symptom-specific effects were direct, whereas the three other symptom-specific effects were indirect and could be explained by effects on other symptoms. Lastly, exploratory analyses showed that the intervention was more effective in improving overall depression severity for participants with higher scores on those four symptoms that were directly affected by the intervention; consequently, the network estimation techniques showed potential in precision psychiatry.
Antidepressants and Hyponatremia
2018, American Journal of Medicine
Bleeding risk under selective serotonin reuptake inhibitor (SSRI) antidepressants: A meta-analysis of observational studies
2017, Pharmacological Research
Citation Excerpt :
The most frequently prescribed antidepressants drugs is selective serotonin reuptake inhibitors (SSRIs) [2]. These drugs have been shown to be effective in major depressive disorder treatment [3], but also generalized anxiety disorder [4] and several other psychiatric diseases [5–8]. They are usually considered to be safer, with a more favorable side-effect profile than previous antidepressants generations [9].
Selective serotonin reuptake inhibitors (SSRIs) have been reported to be potentially associated with an increased risk of bleeding. A meta-analysis of observational studies was conducted to quantify this risk.
Case-control and cohort studies investigating bleeding risk under SSRI therapy were retrieved by searching the Medline, Pascal, Google Scholar and Scopus databases. Case-control studies were included if they reported bleeding incidents with and without the use of SSRIs and cohort studies were included if they reported the rate of bleeds among SSRI users and non-users. The main outcome was severe bleeding, whatever the site. Only data concerning SSRI belonging to the ATC class N06AB were used. For both case-control and cohort studies, we recorded the adjusted effect estimates and their 95% confidence intervals (CI). Pooled adjusted odds ratio (OR) estimates were computed for case-control and cohort studies using an inverse-variance model.
Meta-analysis of the adjusted ORs of 42 observational studies showed a significant association between SSRI use and the risk of bleeding [OR 1.41 (95% CI 1.27–1.57), random effect model, p < 0.0001]. The association was found for the 31 case-control studies (1,255,073 patients), with an increased risk of 41% of bleeding [OR 1.41 (95% CI 1.25–1.60)], as well as for the 11 cohort studies including 187,956 patients [OR 1.36 (95% CI 1.12–1.64)]. Subgroup analyses showed that the association remained constant whatever the characteristics of studies.
This meta-analysis shows an increased risk of bleeding of at least 36% (from 12% to 64%) based on the high-level of observational studies with SSRIs use.
Effect of an educational intervention on the attitudes of the nurses of primary care on depression
2015, Enfermeria Clinica
Describir las actitudes de las enfermeras hacia la depresión, usando un cuestionario estándar para evaluar cómo una intervención formativa influye o modifica estas actitudes.
Estudio prospectivo basado en la aplicación del Depression Attitude Questionnaire, antes y seis meses después de participar en una jornada formativa sobre el rol de enfermería en el manejo de la depresión en atención primaria. La muestra está formada por 40 enfermeras de atención primaria de 10 centros de salud de la provincia de Tarragona.
Las enfermeras se sitúan en una posición neutra en la consideración del manejo de los pacientes deprimidos como una tarea dura, o en sentirse cómodas en la planificación de cuidados, aunque existe un alto grado de aceptación de la afirmación de que el tiempo dedicado a los pacientes deprimidos es gratificante. En general, se han constatado escasas diferencias significativas en las puntuaciones medias en los diferentes ítems del Depression Attitude Questionnaire antes y seis meses después de la intervención formativa.
Se halla, en general, una favorable predisposición hacia el abordaje de la depresión en atención primaria y hacia el papel que pueden ejercer las enfermeras. De este modo, se pueden establecer y prosperar iniciativas formativas y organizativas que puedan perfilar y estructurar más nítidamente el rol de enfermería en el diseño de planes de cuidados dirigidos al paciente deprimido en atención primaria.
To describe nurse attitudes toward depression, using a standardized questionnaire and to evaluate how a training workshop can modify or influence these attitudes.
A prospective study based on the application of the Depression Attitude Questionnaire, before and six months after, participating in a training day on the nursing role in the management of depression in Primary Care. The sample consisted of 40 Primary Care nurses from 10 health centers in the province of Tarragona.
Nurses are in a neutral position when considering the management of depressed patients as a difficult task, or to feel comfortable in this task, but there is a high degree of acceptance of the claim that the time spent caring for depressed patients is rewarding. In general, there was little significant difference in the mean scores for the different items of the Depression Attitude Questionnaire, before and six months, after the training intervention.
The attitude towards the management of depression in Primary Care and to the role that nurses can play in this task is generally favorable. Fruitful training and organizational initiatives can be established in order to define and structure the nursing role in the management of depression in Primary Care.
Ketamine and other potential glutamate antidepressants
2015, Psychiatry Research
The need for rapid acting antidepressants is widely recognised. There has been much interest in glutamate mechanisms in major depressive disorder (MDD) as a promising target for the development of new antidepressants. A single intravenous infusion of ketamine, a N-methyl-d-aspartate (NMDA) receptor antagonist anaesthetic agent, can alleviate depressive symptoms in patients within hours of administration. The mechanism of action appears to be in part through glutamate release onto non-NMDA receptors including α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and metabotropic receptors. However these are also reported effects on 5-HT, dopamine and intracellular effects on the mammalian target of rapamycin (mTOR) pathway. The effects of SSRI (Selective Serotonin Reuptake Inhibitor) antidepressants may also involve alterations in NMDA function. The article reviews the effect of current antidepressants on NMDA and examines the efficacy and mechanism of ketamine. Response to ketamine is also discussed and comparison with other glutamate drugs including lamotrigine, amantadine, riluzole, memantine, traxoprodil, GLYX-13, MK-0657, RO4917523, AZD2066 and Coluracetam. Future studies need to link the rapid antidepressant effects seen with ketamine to inflammatory theories in MDD.
Depression, quality of life and primary care: A cross-sectional study
2013, Journal of Epidemiology and Global Health
To estimate the presence of depression and impairment of quality of life in primary care and identify correlations with demographics and chronic diseases.
500 people (220 men) that visited the Gytheio Health Center, Greece, participated in the study answering a study questionnaire that included demographic and somatometric data, medical history, the Zung self-rating depression scale (SDS-Zung) and the Short Form 12 (SF-12) scale for quality of life evaluation with a mental component scale (MCS) and a physical component scale (PCS).
163 persons (32.6% of the study population) had SDS-Zung scores over 50 indicating depressive symptomatology. Of those 22% of the study population (70% women) had no awareness of their problem and were under no treatment; 80 (16% of the study population) had mild depressive symptoms (SDS-Zung: 53.12 ± 0.6 [95% CI]) and physical impairment: MCS12: 44.32 ± 1.9 (95% CI), PCS: 39.16 ± 2.2 (95% CI) (p < 0.005) and 23 (4.6% of study population) had moderate symptoms (SDS-Zung: 63.82 ± 1.34 [95% CI]), with mental and physical impairment: MCS12: 36.99 ± 1.88 (95% CI), PCS: 34.83 ± 5.12 (95% CI) (p < 0.005) adjusted for age, sex and co-morbidities. Arthritis and COPD were associated with depressive symptomatology and physical impairment (p < 0.05) and coronary heart disease and congestive heart failure with physical impairment (p < 0.005). Patients under anti-depressive medication had significant depressive symptomatology and decreased quality of life (p < 0.0005).
The prevalence of both depressive symptomatology and impairment of quality of life is significant and primary care with simple, validated tools can be the setting for identifying and helping such patients.

View all citing articles on Scopus

^☆: Supported by the John D. and Catherine T. MacArthur Foundation and the Agency for Health Care Policy and Research, San Antonio, Texas.

View full text

ReviewsEfficacy of newer medications for treating depression in primary care patients☆

Abstract

Section snippets

Methods

Results

Discussion

Acknowledgements

Neuropsychopharmacology

J Affect Disord

Depressiona neglected major illness

J Clin Psychiatry

Functioning and well-being outcomes of patients with depression compared with chronic general medical illnesses

Arch Gen Psychiatry

Health care costs associated with depressive and anxiety disorders in primary care

Am J Psychiatry

On the AHCPR depression in primary care guidelinesfurther consideration for practitioners

Am Psychol

Characteristics of patients with major depression who received care in general medical and specialty mental health settings

Med Care

The effects of antidepressive therapy in fibromyalgia syndrome

Fiz Tedavy Rehabil Derg

A random-effects regression model for meta-analysis

Stat Med

sbe23meta-regression

Stata Tech Bull

sbe16meta-analysis

Stata Tech Bull

A note on graphical presentation of estimated odds ratios from several clinical trials

Stat Med

A double-blind comparative study of fluoxetine and dothiepin in the treatment of depression in general practice

Int Clin Psychopharmacol

Paroxetine in the treatment of elderly depressed patients in general practicea double-blind comparison with amitriptyline

Int Clin Psychopharmacol

Treatment of major depression in general practicea double-blind comparison of paroxetine and lofepramine

Br J Clin Pract

The effects of psychomotor performance of fluvoxamine versus mianserin in depressed patients in general practice

Br J Clin Pract

A randomised, double-blind, multi-centre, parallel-group study comparing the tolerability and efficacy of moclobemide and dothiepin hydrochloride in depressed patients in general practice

Int Clin Psychopharmacol

Minaprinean anticholinergic-free antidepressant? Results of a controlled trial of mianserin

Br J Psychiatry

Reviews
Efficacy of newer medications for treating depression in primary care patients☆