New Pharmacological Approaches to the Management of Depression: From Theory to Clinical Practice

1992 ◽  
Vol 26 (1) ◽  
pp. 73-81 ◽  
Author(s):  
Trevor R. Norman ◽  
Fiona K. Judd ◽  
Graham D. Burrows
Keyword(s):  
Side Effects ◽  
Clinical Efficacy ◽  
Antidepressant Treatment ◽  
Antidepressant Drugs ◽  
Phosphodiesterase Inhibitor ◽  
Depressive Illness ◽  
Panic Attacks ◽  
Reversible Inhibitor ◽  
Compulsive Disorder

A review of the clinical efficacy of four structurally distinct antidepressant drugs is presented. Their antidepressant activity can be rationalised within current pharmacological hypotheses of drug action, despite markedly different effects on “in vitro” testing. Fluoxetine, a specific serotonin re-uptake inhibitor, has proven safe, effective treatment for depressive illness and may have a role to play in the treatment of obsessive-compulsive disorder and panic attacks. While it has few of the anticholinergic side effects of the tricyclic antidepressants, nausea, tremor, headache, weight loss, nervousness and sweating are side effects most frequently reported. Minaprine, a compound with weak MAO inhibiting properties and effects on serotonergic receptors, has clinical efficacy in the treatment of depression based on several comparative studies. It is claimed that minaprine lacks anticholinergic and sedative properties. Moclobemide, a specific, reversible inhibitor of MAO-A, has been extensively evaluated in depressive illness. The major advantage of this agent over other irreversible, non-specific MAO inhibitors, is the significant attenuation of the so-called “cheese effect” with doses of tyramine likely to be encountered in foodstuffs. Rolipram, a phosphodiesterase inhibitor, represents a new approach to antidepressant treatment. Limited clinical data suggest that the drug may be an effective antidepressant with few side effects. The place of these agents in therapy is yet to be established.

Guidelines for treating depressive illness with antidepressants: A statement from the British Association for Psychopharmacology

1993 ◽  
Vol 7 (1_suppl) ◽  
pp. 19-23 ◽  
Author(s):  
Stuart A. Montgomery ◽  
P. Bebbington ◽  
P. Cowen ◽  
W. Deakin ◽  
P. Freeling ◽  
...  
Keyword(s):  
Side Effects ◽  
Depressed Mood ◽  
Antidepressant Treatment ◽  
Depressive Illness ◽  
Social Impairment ◽  
Self Blame ◽  
The Core ◽  
The Right ◽  
Therapeutic Doses ◽  
Core Symptoms

Depression is a common illness which affects some 3% of the population per year. At least 25% of those with marked depression do not consult their general practitioner and in half of those who do the illness is not detected. Depression is easy to recognize when four or five of the core symptoms have been present for 2 weeks which often coincides with some occupational and social impairment. The core symptoms are depressed mood, loss of interest or pleasure, loss of energy or fatigue, concentration difficulties, appetite disturbance, sleep disturbance, agitation or retardation, worthlessness or self blame and suicidal thoughts. A diagnosis of depression is made when five of these core symptoms, one of which should be depressed mood or loss of interest or pleasure, have been present for 2 weeks. Four core symptoms are probably sufficient. Response to antidepressants is good in those with more than mild symptoms. When there are only few or very mild depressive symptoms evidence of response to antidepressants is more uncertain. Antidepressants are effective, they are not addictive and do not lose efficacy with prolonged use. The newer antidepressants have fewer side effects than the older tricyclics, they are better tolerated and lead to less withdrawals from treatment. They are less cardiotoxic and are safer in overdose. Antidepressants should be used at full therapeutic doses. Treatment failure is often due to too low a dose being used in general practice. It may be difficult to reach the right dose with the older tricyclics because of side effects. To consolidate response, treatment should be continued for at least 4 months after the patient is apparently well. Stopping the treatment before this is ill-advised as the partially treated depression frequently returns. Most depression is recurrent. Long-term antidepressant treatment is effective in reducing the risk of new episodes of depression and should be continued to keep the patient well.

scholarly journals Antidepressant drugs and sexual dysfunction

2013 ◽  
Vol 202 (6) ◽  
pp. 396-397 ◽  
Author(s):  
David S. Baldwin ◽  
Thomas Foong
Keyword(s):  
Depressive Symptoms ◽  
Sexual Dysfunction ◽  
Sexual Function ◽  
Antidepressant Treatment ◽  
Antidepressant Drugs ◽  
Self Esteem ◽  
Depressive Illness ◽  
Controlled Trials

SummaryDepressive symptoms and depressive illness are associated with impairments in sexual function and satisfaction but the findings of randomised placebo-controlled trials demonstrate that antidepressant drugs can be associated with the development or worsening of sexual dysfunction. Sexual difficulties during antidepressant treatment often resolve as depression lifts but may persist over long periods, and can reduce self-esteem and affect mood and relationships adversely. Sexual dysfunction during antidepressant treatment is typically associated with many possible causes, but the risk of dysfunction varies with differing antidepressants, and should be considered when selecting an antidepressant.

Secondary sexual dysfunction with antidepressant treatment: Study on 50 patients

2016 ◽  
Vol 33 (S1) ◽  
pp. S591-S591
Author(s):  
O.W. Muquebil Ali Al Shaban Rodriguez ◽  
S. Ocio León ◽  
M. Gómez Simón ◽  
M.J. Hernández González ◽  
E. Álvarez de Morales Gómez-Moreno ◽  
...  
Keyword(s):  
Side Effects ◽  
Sexual Dysfunction ◽  
Treatment Adherence ◽  
Antidepressant Treatment ◽  
Antidepressant Drugs ◽  
Sexual Side Effects ◽  
Competing Interest ◽  
The Relationship ◽  
Transversal Study

IntroductionThe side effects of the various antidepressant drugs on the sexual field (with very few exceptions) are well known, and they affect the quality of life in important manners. The incidence rate, communicated spontaneously by the patient, has been estimated around 10–15%, and can reach amounts of 50–60% with SSRIs when studied specifically. It has been suggested that these effects compromise treatment adherence.ObjectivesTo estimate the incidence and intensity of the side effects on the sexual field with different antidepressants, as well as its relationship with treatment adherence.MethodologyTransversal study on 50 patients assisted in medical consultation. Collection of data in office (October 2014–October 2015).Administration of survey PRSexDQ-SALSEX. In order to research the relationship with treatment adherence, one question surveyed the patient whether he/she had thought about finishing treatment for this reason.ResultsTwenty-nine patients (58% of the sample) presented some degree of sexual dysfunction. Five individuals (17.2%) communicated it spontaneously. Nine individuals (31%) responded that they did not accept positively the changes in their sexual field, and they had thought about withdrawing treatment for this reason. They were given the test of self-compliance statement (Haynes-Sackett), with a result of four non-compliant (44.4%). The most frequently involved drugs were fluoxetine (n = 5, 10% of the sample total) and paroxetine (n = 4, 8%).ConclusionsThe high impact of sexual side effects with a low rate of spontaneous communication coincides with previous existent studies.Limitation when estimating adhesion due to methodological difficulties in the design of the study. However, high impression by using the selected method of determination.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Combinations of Antidepressant Drugs in the Treatment of Depressive Illness

1973 ◽  
Vol 18 (5) ◽  
pp. 399-402 ◽  
Author(s):  
I. Ray
Keyword(s):  
Side Effects ◽  
Psychotropic Drugs ◽  
Global Assessment ◽  
Antidepressant Drugs ◽  
Depressive Illness ◽  
Considerable Improvement ◽  
Results Of Treatment

Seventy-three inpatients and 11 outpatients, aged 16-76, were treated with modified sleep, combined antidepressant drugs and ECT. Every patient had treatment with psychotropic drugs prior to referral to the Yorkton Psychiatric Centre. Side effects encountered during the treatment were minimal. Concomitant ECT was also used with combined antidepressant drugs, and recovery of all patients from anesthesia during ECT was uneventful. Results of treatment on global assessment showed considerable improvement in 52 patients, 30 improved, and no change in 2 patients. The average stay in hospital was 19.5 days.

Beyond the monoamine hypothesis: mechanisms, molecules and methods

2002 ◽  
Vol 17 (S3) ◽  
pp. 294s-299s ◽  
Author(s):  
I. Hindmarch
Keyword(s):  
Tricyclic Antidepressants ◽  
Rating Scales ◽  
Stress Disorder ◽  
Antidepressant Drugs ◽  
Antidepressant Activity ◽  
Hippocampal Volume ◽  
Depressive Illness ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Noradrenaline Levels

SummaryThe first effective antidepressants (monoamine oxidase inhibitors and tricyclic antidepressants) relied on their ability to augment serotonin and noradrenaline levels at the synapse. Forty years later, the same biological model led to the supremacy of the serotonergic hypothesis to explain not only the pathophysiology of depressive illness, but also the neuropharmacological basis for obsessive compulsive disorder, phobias, posttraumatic stress disorder, and even generalized anxiety disorder. It could be argued that the blinkered view of depression as a solely serotonergic phenomenon has not only restrained and limited research into other potential systems, but has also slowed down the discovery of putative antidepressant drugs. While some might argue that the hypothalamic-pituitary-adrenal (HPA) axis explains an individual’s sensitivity to depression, there are others who equally claim that the most likely explanations are to be found in the neuropsychopharmacology of the immune system or even through reductions in hippocampal volume. There is a richness of possibilities regarding the mechanisms for antidepressant activity embracing theoretical, pharmacological and clinical data. However, the methods by which putative antidepressants are assessed and their clinical efficacy demonstrated are not always robust. That current clinical comparisons of antidepressants rarely show major differences in efficacy between existing molecules could be taken as an indication that “all drugs are the same” or perhaps, more insightfully, as an indication that the ubiquitous Hamilton depression (HAM-D) rating scales are not sensitive to inter-drug differences, even though pronounced pharmacodynamic differences between molecules are easily demonstrated. Any advances in the development of new antidepressants will have to find not only original compounds but also unique psychometric tests by which the drugs can be assessed in a sensitive, reliable, and valid manner.

scholarly journals Reduced Treatment-Emergent Sexual Dysfunction as a Potential Target in the Development of New Antidepressants

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
David S. Baldwin ◽  
M. Carlotta Palazzo ◽  
Vasilios G. Masdrakis
Keyword(s):  
Sexual Dysfunction ◽  
Antidepressant Treatment ◽  
Antidepressant Drugs ◽  
Well Being ◽  
Self Esteem ◽  
Depressive Illness ◽  
Current Management ◽  
Human Relationships ◽  
Management Approaches ◽  
Phosphodiesterase 5

Pleasurable sexual activity is an essential component of many human relationships, providing a sense of physical, psychological, and social well-being. Epidemiological and clinical studies show that depressive symptoms and depressive illness are associated with impairments in sexual function and satisfaction, both in untreated and treated patients. The findings of randomized placebo-controlled trials demonstrate that most of the currently available antidepressant drugs are associated with the development or worsening of sexual dysfunction, in a substantial proportion of patients. Sexual difficulties during antidepressant treatment often resolve as depression lifts but can endure over long periods and may reduce self-esteem and affect mood and relationships adversely. Sexual dysfunction during antidepressant treatment is typically associated with many possible causes, but the risk and type of dysfunction vary with differing compounds and should be considered when making decisions about the relative merits and drawbacks of differing antidepressants. A range of interventions can be considered when managing patients with sexual dysfunction associated with antidepressants, including the prescription of phosphodiesterase-5 inhibitors, but none of these approaches can be considered “ideal.” As treatment-emergent sexual dysfunction is less frequent with certain drugs, presumably related to differences in their pharmacological properties, and because current management approaches are less than ideal, a reduced burden of treatment-emergent sexual dysfunction represents a tolerability target in the development of novel antidepressants.

Pharmacotherapy, ECT, and TMS

2014 ◽  
Author(s):  
Jessica Ann Stewart ◽  
L. Mark Russakoff ◽  
Jonathan W. Stewart
Keyword(s):  
Side Effects ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Psychotic Disorders ◽  
Premenstrual Dysphoric Disorder ◽  
Depressive Illness ◽  
Mood Stabilizers ◽  
Close Monitoring ◽  
Antipsychotic Medications ◽  
Compulsive Disorder ◽  
Primary Indication

Physicians’ attention to patients’ concerns and attitudes about taking medication will engender adherence, as will close monitoring of potentially disconcerting side effects. The primary indication for antipsychotic medications is the treatment of psychotic disorders and mania, even in the absence of psychosis. The more troublesome side effects of antipsychotic medications include increased appetite and weight gain; extrapyramidal side effects, tardive dyskinesia, and neuroleptic malignant syndrome. Antidepressants are effective for treating depressive illness, including major depression, persistent depressive disorder (dysthymia) and premenstrual dysphoric disorder. They are also often used effectively in the treatment of anxiety disorders, obsessive-compulsive disorder, bulimia nervosa, and somatic symptom disorders. Selective serotonin reuptake inhibitors (SSRIs) are generally well tolerated. Other important categories of medications include mood stabilizers and anxiolytics.

A New Depression Scale Designed to be Sensitive to Change

1979 ◽  
Vol 134 (4) ◽  
pp. 382-389 ◽  
Author(s):  
Stuart A. Montgomery ◽  
Marie Åsberg
Keyword(s):  
Clinical Trials ◽  
Rating Scale ◽  
Antidepressant Treatment ◽  
Antidepressant Drugs ◽  
Depression Scale ◽  
Depressive Illness ◽  
Sensitivity To Change ◽  
Ethical Implications ◽  
Hamilton Rating Scale ◽  
Better Than

SummaryThe construction of a depression rating scale designed to be particularly sensitive to treatment effects is described. Ratings of 54 English and 52 Swedish patients on a 65 item comprehensive psychopathology scale were used to identify the 17 most commonly occurring symptoms in primary depressive illness in the combined sample.Ratings on these 17 items for 64 patients participating in studies of four different antidepressant drugs were used to create a depression scale consisting of the 10 items which showed the largest changes with treatment and the highest correlation to overall change.The inter-rater reliability of the new depression scale was high. Scores on the scale correlated significantly with scores on a standard rating scale for depression, the Hamilton Rating Scale (HRS), indicating its validity as a general severity estimate. Its capacity to differentiate between responders and non-responders to antidepressant treatment was better than the HRS, indicating greater sensitivity to change. The practical and ethical implications in terms of smaller sample sizes in clinical trials are discussed.

A Comparative Ex Vivo Study of Plasminogen Activators and Proteases for Fibrinolytic Activity and Side Effects in Rabbits

1977 ◽  
Vol 37 (01) ◽  
pp. 154-161 ◽  
Author(s):  
B. A Janik ◽  
S. E Papaioannou
Keyword(s):  
Side Effects ◽  
Effective Dose ◽  
Fibrinolytic Activity ◽  
Ex Vivo ◽  
Plasminogen Activators ◽  
Assay System ◽  
Coagulation Parameters ◽  
Ex Vivo Assay

SummaryUrokinase, streptokinase, Brinase, trypsin, and SN 687, a bacterial exoprotease, have been evaluated in an ex vivo assay system. These enzymes were injected into rabbits and the fibrinolytic activity as well as other coagulation parameters were measured by in vitro techniques. Dose-response correlations have been made using the euglobulin lysis time as a measure of fibrinolytic activity and the 50% effective dose has been determined for each enzyme. Loading doses, equal to four times the 50% effective dose, were administered to monitor potential toxicity revealing that Brinase, trypsin, and SN 687 were very toxic at this concentration.Having established the 50% effective dose for each enzyme, further testing was conducted where relevant fibrinolytic and coagulation parameters were measured for up to two days following a 50% effective dose bolus injection of each enzyme. Our results have demonstrated that urokinase and streptokinase are plasminogen activators specifically activating the rabbit fibrinolytic system while Brinase, trypsin and SN 687 increase the general proteolytic activity in vivo.The advantages of this ex vivo assay system for evaluating relative fibrinolytic potencies and side effects for plasminogen activators and fibrinolytic proteases have been discussed.

Mechanism of the Antiplatelet Action of Dipyridamole in Whole Blood: Modulation of Adenosine Concentration and Activity

1986 ◽  
Vol 55 (01) ◽  
pp. 012-018 ◽  
Author(s):  
Paolo Gresele ◽  
Jef Arnout ◽  
Hans Deckmyn ◽  
Jos Vermylen
Keyword(s):  
Platelet Aggregation ◽  
Adenosine Receptor ◽  
Whole Blood ◽  
Blood Cells ◽  
Inhibitory Action ◽  
Phosphodiesterase Inhibitor ◽  
Inhibitory Effect ◽  
Adenosine Concentration ◽  
Pharmacological Studies

SummaryDipyridamole inhibits platelet aggregation in whole blood at lower concentrations than in plasma. The blood cells responsible for increased effectiveness in blood are the erythrocytes. Using the impedance aggregometer we have carried out a series of pharmacological studies in vitro to elucidate the mechanism of action of dipyridamole in whole blood. Adenosine deaminase, an enzyme breaking down adenosine, reverses the inhibitory action of dipyridamole. Two different adenosine receptor antagonists, 5’-deoxy-5’-methylthioadenosine and theophylline, also partially neutralize the activity of dipyridamole in blood. Enprofylline, a phosphodiesterase inhibitor with almost no adenosine receptor antagonistic properties, potentiates the inhibition of platelet aggregation by dipyridamole. An inhibitory effect similar to that of dipyridamole can be obtained combining a pure adenosine uptake inhibitor (RE 102 BS) with a pure phosphodiesterase inhibitor (MX-MB 82 or enprofylline). Mixing the blood during preincubation with dipyridamole increases the degree of inhibition. Lowering the haematocrit slightly reduces the effectiveness.Although we did not carry out direct measurements of adenosine levels, the results of our pharmacological studies clearly show that dipyridamole inhibits platelet aggregation in whole blood by blocking the reuptake of adenosine formed from precursors released by red blood cells following microtrauma. Its slight phosphodiesterase inhibitory action potentiates the effects of adenosine on platelets.

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