Pharmacological Treatments for Unipolar Depression

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

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

scholarly journals Clinical trials of antidepressant medications are producing meaningless results

2003 ◽  
Vol 183 (2) ◽  
pp. 102-104 ◽  
Author(s):  
Gordon Parker ◽  
Ian M. Anderson ◽  
Peter Haddad
Keyword(s):  
Clinical Trials ◽  
Antidepressant Treatment ◽  
Meta Analysis ◽  
Antidepressant Medication ◽  
Unipolar Depression ◽  
Controlled Trials ◽  
Antidepressant Medications ◽  
Treatment Of Depression ◽  
Randomised Controlled ◽  
The Uk

A recent alert from the UK Committee on Safety of Medicines stated that the dangers of treatment of depression with paroxetine outweigh the benefits in those under 18. Such a warning should focus our minds on the evidence on which clinical practice is based. Antidepressant treatment of depression in the under-18s has been thought to be justified because clinical trials show that it works so well in over-18s. But is that a reasonable assessment of the evidence? Kirsch et al (2002) use the analogy of ‘The Emperor's New Clothes' to describe the findings from their meta-analysis of randomised placebo-controlled trials of antidepressants. They conclude that antidepressant medication appears to have only a small effect on outcome over and above placebo. In this analogy psychiatry is the emperor, drug trials are the fraudsters and the deception is being revealed by a growing body of critical opinion proposing that, once methodological problems with clinical trials are taken into account, antidepressants either do not work at all or have an effect that is so small as to be clinically unimportant (Andrews, 2001; Moncrieff, 2002). A large number of randomised placebo-controlled trials of antidepressants have been carried out over the past decades, mostly funded by the pharmaceutical industry, and it is now recognised that about 50% of negative trials go unpublished (Thase, 1999). Meanwhile, unipolar depression has jumped into the top five of the world's total burden of disease, and there is an imperative need for effective and safe treatments. Do we need more randomised controlled trials (RCTs) of antidepressant medications, or has that research paradigm outlived its usefulness? In this month's debate, Professor Gordon Parker, University of New South Wales and Black Dog Institute, Australia, and Drs Ian Anderson and Peter Haddad from the University of Manchester discuss whether clinical trials for antidepressant medication produce meaningless results.

Sexual Dysfunction in Major Depression

CNS Spectrums ◽  
2006 ◽  
Vol 11 (S9) ◽  
pp. 19-23 ◽  
Author(s):  
Katherine Williams ◽  
Margaret F. Reynolds
Keyword(s):  
Major Depression ◽  
Sexual Dysfunction ◽  
Antidepressant Medication ◽  
Unipolar Depression ◽  
Future Research ◽  
Drug Induced ◽  
Depression Disorders ◽  
Severity Of Depression ◽  
Loss Of Libido ◽  
Disorders Of Arousal

AbstractLittle is known about the prevalence, typology, and natural course of non—drug-induced sexual dysfunction in patients with depression. Loss of libido has been reported in various studies to affect from 25% to 75% of patients with unipolar depression, and its prevalence appears to be correlated with the severity of depression. Disorders of arousal also appear to be relatively common in both men and women with major depression, of whom ~25% may experience problems with erection or lubrication. The scant available data regarding orgasmic difficulties in patients with depression who have not yet taken antidepressant medication suggest that they are more common than in the general population. The potential causes of sexual dysfunction in patients with depression are complex and little investigated, and future research must distinguish and explore the various biological, psychological, and psychosocial factors that are likely to be involved.

Comparative Efficacy and Safety of Sertraline Versus Nortriptyline in Major Depression in Patients 70 and Older

1999 ◽  
Vol 11 (1) ◽  
pp. 85-99 ◽  
Author(s):  
Sanford I. Finkel ◽  
Ellen M. Richter ◽  
Cathryn M. Clary
Keyword(s):  
Major Depression ◽  
Rating Scale ◽  
Antidepressant Treatment ◽  
Change Score ◽  
Attrition Rate ◽  
Double Blind ◽  
Almost All ◽  
Positive Effect ◽  
Population Segment

Background. Few randomized, double-blind studies that examine antidepressant treatment in patients 70 years and older are available. To provide additional data on the safety and efficacy of antidepressants in this rapidly growing population segment, a subgroup analysis of a larger sertraline vs. nortriptyline elderly depression treatment study was performed. Methods. Outpatients (N = 76) who met DSM-III-R criteria for major depression with a minimum Hamilton Depression Rating Scale (HAM-D) severity score of 18 were randomized to 12 weeks of flexible dose treatment with sertraline (50–150 mg) or nortriptyline (25–100 mg). Results. Both treatments significantly improved depression as measured by the HAM-D and Clinical Global Impression scales. At Weeks 10, 12, and endpoint, sertraline demonstrated a significantly greater reduction in depression severity compared to nortriptyline as measured by improvement on the 24-item HAM-D (mean adjusted change score of 14.8 vs. 7.6, respectively, at Week 12; p = .001). Sixty-five percent of sertraline-treated patients were responders by Week 12 (50% or greater reduction from baseline in 24-item HAM-D score) compared to 26% of nortriptyline-treated patients (p < .05). Sertraline treatment had a significantly more positive effect, when compared to nortriptyline, across almost all associated measures of cognitive function, energy, anxiety, and quality of life and was better tolerated than nortriptyline, with a lower attrition rate/side effect burden. Conclusion. The efficacy advantage of sertraline appeared to be even greater in this subgroup of older patients drawn from a larger treatment study of depression that included elderly individuals over the age of 60.

Placebo-Controlled Trial of Lithium Augmentation of Fluoxetine and Lofepramine

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

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

scholarly journals Item-based analysis of the effects of duloxetine in depression: a patient-level post hoc study

2019 ◽  
Vol 45 (3) ◽  
pp. 553-560 ◽  
Author(s):  
Alexander Lisinski ◽  
Fredrik Hieronymus ◽  
Jakob Näslund ◽  
Staffan Nilsson ◽  
Elias Eriksson
Keyword(s):  
Depressed Mood ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Rating Scale ◽  
Early Response ◽  
Controlled Trials ◽  
Early Effect ◽  
Patient Level ◽  
Response Profile ◽  
Effect Parameter ◽  
Meta Analyses

Abstract Oft-cited trial-level meta-analyses casting doubt on the usefulness of antidepressants have been based on re-analyses of to what extent the active drug has outperformed placebo in reducing the sum score of the Hamilton Depression Rating Scale (HDRS-17-sum) in clinical trials. Recent studies, however, suggest patient-level analyses of individual HDRS items to be more informative when assessing the efficacy of an antidepressant. To shed further light on both symptom-reducing and symptom-aggravating effects of a serotonin and noradrenaline reuptake inhibitor, duloxetine, when used for major depression in adults, we hence applied this approach to re-analyse data from 13 placebo-controlled trials. In addition, using patient-level data from 28 placebo-controlled trials of selective serotonin reuptake inhibitors (SSRIs), the response profile of duloxetine was compared to that of these drugs. Duloxetine induced a robust reduction in depressed mood that was not dependent on baseline severity and not caused by side-effects breaking the blind. A beneficial effect on depressed mood was at hand already after one week; when outcome was assessed using HDRS-17-sum as effect parameter, this early response was however masked by a concomitant deterioration with respect to adverse event-related items. No support for a suicide-provoking effect of duloxetine was obtained. The response profile of duloxetine was strikingly similar to that of the SSRIs. We conclude that the use of HDRS-17-sum as effect parameter underestimates the true efficacy and masks an early effect of duloxetine on core symptoms of depression. No support for major differences between duloxetine and SSRIs in clinical profile were obtained.

scholarly journals Antidepressant study design affects patient expectancy: a pilot study

2009 ◽  
Vol 40 (5) ◽  
pp. 781-788 ◽  
Author(s):  
B. Rutherford ◽  
J. Sneed ◽  
D. Devanand ◽  
R. Eisenstadt ◽  
S. Roose
Keyword(s):  
Rating Scale ◽  
Antidepressant Medication ◽  
Group Differences ◽  
Controlled Trials ◽  
Group Assignment ◽  
Treatment Conditions ◽  
Treatment Of Depression ◽  
Before And After ◽  
Hamd Score ◽  
Pilot Rct

BackgroundResponse to antidepressant medication is higher in comparator versus placebo-controlled randomized controlled trials (RCTs). Patient expectancy is an important influence on clinical outcome in the treatment of depression and may explain this finding. The results are reported from a pilot RCT studying expectancy and depression outcome in placebo-controlled versus comparator treatment conditions.MethodOut-patients aged 18–65 years with major depressive disorder (MDD) were enrolled in this 8-week RCT. Subjects were randomized to placebo-controlled (escitalopram or placebo) or comparator (escitalopram or citalopram) administration of antidepressant medication. Subjects reported their expected likelihood and magnitude of depression improvement before and after randomization using questions from the Credibility and Expectancy Scale (CES). A regressed change model of post-randomization expectancy of improvement was fit to the data to determine whether subjects in the comparator group reported greater expectancies of improvement than subjects in the placebo-controlled group.ResultsTwenty subjects with mean age 56.5±11.7 years, a baseline Hamilton Depression Rating Scale (HAMD) score of 24.2±5.3, baseline Beck Depression Inventory (BDI) score of 24.9±6.4 and baseline Clinical Global Impressions (CGI) – Severity score of 4.0±0.3 were enrolled in the study. Adjusting for other factors, the effect of group assignment on expected magnitude of improvement was significant and large (effect size 1.5). No group differences in expected likelihood of improvement were found.ConclusionsRandomization to comparator versus placebo-controlled administration of antidepressant medication produced greater expectancies of how much patients would improve during the trial. This expectancy difference may explain the higher response and remission rates that are observed in comparator versus placebo-controlled trials.

Recent Developments in Geriatric Psychopharmacotherapy

1994 ◽  
Vol 39 (8_suppl) ◽  
pp. 9-18 ◽  
Author(s):  
Alastair J. Flint
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Antidepressant Treatment ◽  
Bipolar Affective Disorder ◽  
Unipolar Depression ◽  
The Elderly ◽  
Blood Levels ◽  
Pharmacological Management ◽  
Treatment Of Depression ◽  
Recent Developments ◽  
Psychiatric Complications

This paper highlights recent advances in the pharmacological management of geriatric affective disorders and dementia. The current roles of tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) in the treatment of depression in old age are discussed. Recent findings pertaining to continuation and maintenance of antidepressant treatment are also addressed. The treatment of bipolar affective disorder in the elderly has received much less study than has unipolar depression. A number of issues relating to efficacy, side-effects and optimal blood levels of lithium, carbamazepine and valproate in bipolar disorder remain unresolved and await further study. Finally, drug treatment of the cognitive impairment and psychiatric complications of Alzheimer's disease is reviewed.

Clinical status after two-weeks of antidepressant treatment: A prognostic factor in unipolar major depression?

2016 ◽  
Vol 33 (S1) ◽  
pp. S409-S409
Author(s):  
I. Domínguez ◽  
L. Nuño ◽  
G. Oriolo ◽  
R. Quintero ◽  
V. Navarro ◽  
...  
Keyword(s):  
Major Depression ◽  
Pharmacological Treatment ◽  
Depressive Episode ◽  
Antidepressant Treatment ◽  
Clinical Status ◽  
Treatment Protocol ◽  
Unipolar Depression ◽  
Therapeutic Decisions ◽  
Competing Interest ◽  
Unipolar Major Depression

Although most unipolar depression clinical guidelines advise against evaluating the efficacy of antidepressant pharmacological treatment until it has been administered in therapeutic doses for a minimum of 4–6 weeks, there is an increasing tendency to make therapeutic decisions after only 2 weeks of treatment. We present a study which aim is to determine whether the clinical course, following 2 weeks of antidepressant treatment, allows therapeutic decisions to be made for patients affected by a moderate/severe depressive episode. The study has an 8-week, prospective, observational design in which all consecutive in- and outpatients with moderate/severe unipolar major depression aged over 17 years received antidepressant treatment based on a standardized treatment protocol. Clinical status was assessed at baseline and at 2-, 4-, and 8-weeks. The final sample consisted of a total of 114 subjects. In our sample, the rate of remitters versus non-remitters was similar between the 2-week improvers and the 2-week non-improvers. It should also be emphasized that it was not possible to explain, based on the epidemiological and clinical characteristics assessed, which 2-week non-improvers would tend towards remission and which would show a partial or full response. Based on these results, for patients affected by a moderate/severe unipolar depressive episode, it would not be appropriate to make new therapeutic decisions following 2 weeks of anti-depressive pharmacological treatment depending on whether the patient has shown clinical improvement or not.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Must we fear antidepressants in adolescents?

2017 ◽  
Vol 41 (S1) ◽  
pp. S450-S451
Author(s):  
S. Paulino ◽  
N. Santos ◽  
A.C. Almeida
Keyword(s):  
Major Depression ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Antidepressant Treatment ◽  
Good Deal ◽  
Epidemiological Studies ◽  
Scientific Data ◽  
The Media ◽  
Media Hype ◽  
Competing Interest

IntroductionEpidemiological studies have established that teenager's prevalence rates of major depression are significant (10%). The media has given a good deal of attention to the potential risks of antidepressants and their connection to increased suicidality (especially in children and adolescents). These concerns have had a significant impact on both the prescribing of antidepressants and the parental fears about their use. It is interesting to note that in large groups’ studies of adolescents treated with selective serotonin reuptake inhibitors there have been no evidence of increased suicidal risk.ObjectiveUnderstand if there is a significant association between antidepressant treatment and suicidality in a 3-months follow-up study of the adolescent's consultation of Centro Hospitalar Lisboa Norte.MethodsAnalysis of 81 adolescents with an initial diagnosis of major depression treated with an antidepressant for at least 3 months.ResultsAfter the follow-up period there has been an improvement in sadness in 92.6% of the adolescents, a remission of death thoughts in 98.8% and an absence of suicides attempts. In 61.7%, it was necessary to introduce also an antipsychotic in a low dose and in 12.3% another antidepressant with a hypnotic effect.ConclusionIt is clear that untreated major depression carries significant suffering and disability. Although treatment with antidepressants may take several weeks before clinical improvement appear and depression may worsen in the first days, its therapeutic effect should not be underestimated even if becomes necessary to add another medication in the first days. In evaluating these kinds of concerns, we must always differentiate between media hype and scientific data.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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