Antidepressant Use by Class: Association with Major Adverse Cardiac Events in Patients with Coronary Artery Disease.

BACKGROUND: To assess use of antidepressants by class in relation to cardiology practice recommendations, and the association of antidepressant use with the occurrence of major adverse cardiovascular events (MACE) including death. METHODS: This is a historical cohort study of all patients who completed cardiac rehabilitation (CR) between 2002 and 2012 in a major CR center. Participants completed the Patient Health Questionnaire (PHQ-9) at the start and end of the program. A linkage system enabled ascertainment of antidepressant use and MACE through 2014. RESULTS: There were 1,694 CR participants, 1,266 (74.7%) of whom completed the PHQ-9 after the program. Depressive symptoms decreased significantly from pre- (4.98 ± 5.20) to postprogram (3.57 ± 4.43) (p < 0.001). Overall, 433 (34.2%) participants were on antidepressants, most often selective serotonin reuptake inhibitors (SSRI; n = 299; 23.6%). The proportion of days covered was approximately 70% for all 4 major antidepressant classes; discontinuation rates ranged from 37.3% for tricyclics to 53.2% for serotonin-norepinephrine reuptake inhibitors (SNRI). Antidepressant use was significantly associated with lower depressive symptoms after CR (before, 7.33 ± 5.94 vs. after, 4.69 ± 4.87; p < 0.001). After a median follow-up of 4.7 years, 264 (20.9%) participants had a MACE. After propensity matching based on pre-CR depressive symptoms among other variables, participants taking tricyclics had significantly more MACE than those not taking tricyclics (HR = 2.46; 95% CI 1.37-4.42), as well as those taking atypicals versus not (HR = 1.59; 95% CI 1.05-2.41) and those on SSRI (HR = 1.45; 95% CI 1.07-1.97). There was no increased risk with use of SNRI (HR = 0.89; 95% CI 0.43-1.82). CONCLUSION: The use of antidepressants was associated with lower depression, but the use of all antidepressants except SNRI was associated with more adverse events.

Impact of drug therapy on brachioradial pruritus.

Few studies have described therapeutic options in brachioradial pruritus. We describe a cross-sectional study of brachioradial pruritus patients treated in an outpatient unit. We reviewed medical records and interviewed brachioradial pruritus patients without indication for decompressive surgery, in order to access the perceptions of intensity of pruritus prior to treatment and response to therapy. We found that antidepressants and anticonvulsants were the most frequently prescribed drugs. Best reductions in pruritus were associated with its highest intensities prior to treatment, and with longer periods of therapy.

Impact of drug therapy on brachioradial pruritus

Abstract: Few studies have described therapeutic options in brachioradial pruritus. We describe a cross-sectional study of brachioradial pruritus patients treated in an outpatient unit. We reviewed medical records and interviewed brachioradial pruritus patients without indication for decompressive surgery, in order to access the perceptions of intensity of pruritus prior to treatment and response to therapy. We found that antidepressants and anticonvulsants were the most frequently prescribed drugs. Best reductions in pruritus were associated with its highest intensities prior to treatment, and with longer periods of therapy.

[Psychopharmacological treatments in childhood and adolescence]. / Psychopharmaka im Kindes- und Jugendalter.

Compared to adults, the use of psychopharmacological substances in childhood and adolescence is significantly more controversial. Often sensation-seeking media reports on the negative effects of psychopharmacological treatments of children and adolescents intensify this controversy on a regular basis. In addition, even pharmacologically trained experts--though frequently without expertise in Child and Adolescent Psychiatry--question the seriousness and thus the demands for treatment of psychiatric disorders in childhood and adolescence. Considering this background evidence based treatment decisions in pediatric psychopharmacology are of utmost importance. Effective psychopharmacotherapy needs to be distinguished from ineffective treatments. The pros and cons of such evidence based treatment approaches ought to be weighted out carefully together with the patients and their families. The aim of this article is to provide a rational and concise foundation for the use of psychopharmacotherapy for clinicians treating children and adolescents as well as to point out the currently best evidence for psychopharmacological treatments of selected disorders in child and adolescent psychiatry.

Fármacos antidepresivos / Antidepressive drugs

Los síndromes depresivos son frecuentes en la población general pero pasan, muchas veces, inadvertidos cuando se trata de cuadros larvados. Los recursos farmacológicos actualmente disponibles son numerosos pero son frecuentemente mal utilizados (tipos, dosis y tiempo), sin la prudencia necesaria y sin observar las indicaciones establecidas.

Side-effect profile of fluoxetine in comparison with other SSRIs, tricyclic and newer antidepressants: a meta-analysis of clinical trial data.

BACKGROUND: In the last ten years, SSRIs have increasingly replaced TCAs as comparators of newer antidepressants (ADs), because of their better tolerability profile. In particular, fluoxetine has become a reference drug for the treatment of depression, but the occurrence of individual side effects in depressed subjects treated with fluoxetine and each comparator AD have not been systematically investigated. METHODS: This meta-analysis investigated the frequency of side effects induced by fluoxetine or alternative ADs and compared the occurrence of individual side effects in depressed subjects. All randomised clinical trials (RCTs) comparing fluoxetine with any other AD drug in patients with major depression were located by searching the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Controlled Trials Register. Two reviewers independently extracted information. RESULTS: Significantly less percentage of patients treated with fluoxetine experienced any side effects in comparison with TCAs (50.9 % vs 60.3 %, 29 RCTs; RR = 0.84, p = 0.003), but not in comparison with other SSRIs (59.4 % vs 59.3 %, 15 RCTs; RR = 1.00, p = 0.902). In addition, fluoxetine was better tolerated in comparison with TCAs and related ADs (RR 0.61, 95 % CI 0.52, 0.71), but not in comparison with other SSRIs. Regard to individual side effects, activating (insomnia, agitation, tremor and anxiety) and gastrointestinal adverse events (nausea, vomiting, diarrhoea, weight loss and anorexia) were significantly more frequent in fluoxetine-treated patients, whereas cholinergic side effects were significantly less frequent. CONCLUSIONS: Fluoxetine compared to other ADs had more activating and gastrointestinal adverse effects, which often require additional pharmacotherapy or other managements strategies, leading to discontinuation and non-compliance and increasing the costs. This information is relevant to base on evidence the prescription of ADs in everyday clinical practice.

Non-stimulant medications in the treatment of ADHD.

BACKGROUND: Stimulants are the first-line medication in the psychopharmacological treatment of attention-deficit hyperactivity disorder (ADHD). However, 10 to 30% of all children and adults with ADHD either do not respond to or do not tolerate treatment with stimulants. OBJECTIVE: To describe alternative treatment approaches with various non-stimulant agents, especially atomoxetine. METHOD: General review of empirically based literature concerning efficacy and safety of the substances. RESULTS: A large and still increasing body of data supports the usefulness of atomoxetine, a once daily dosing, and new selective noradrenalin reuptake inhibitor, with few side effects. Atomoxetine has been licensed in the US for use in ADHD across the lifespan, and is currently under consideration in Europe. Other non-stimulant substances, such as tricyclic antidepressants (TCAs) and alpha-2-adrenergic agonists, which are used to treat ADHD, are also reviewed. TCAs have been well studied and shown to be efficacious in the treatment of ADHD, but are limited by side effects. The number of studies documenting the efficacy of alpha-2-adrenergic agonists is still limited. Some experimental studies support a potential role of cholinergic drugs such as acetylcholinesterase inhibitors (tacrine, donepezil) as well as novel nicotinic analogues (ABT-418). CONCLUSION: Non-stimulant agents have been shown to be effective in treatment of ADHD. Especially, atomoxetine seems promising and newline drugs are in development.

Antidepressants in the treatment of irritable bowel syndrome and visceral pain syndromes.

Irritable bowel syndrome (IBS) is characterized by abdominal pain associated with disordered defecation, which may include urgency and altered stool frequency. Visceral pain syndromes, including IBS, may be effectively treated by a variety of therapies that modulate the interactions between the central and enteric nervous systems. Clinical observations and preliminary data suggest that antidepressants may be efficacious for the treatment of these syndromes. The tricyclic antidepressants (TCAs) have been utilized most extensively in this area, but there is a need for more rigorous efficacy data. Serotonin, an important neurotransmitter in both the central and enteric nervous systems, modifies both motility and sensation in the gut. Recognition of the importance of serotonin in digestive motility and sensation has sparked interest in the use of agents that modify serotonergic transmission in visceral pain syndromes. Pharmacological therapeutics that modulate the biological amines (serotonin, norepinephrine, dopamine and catecholamines) both peripherally and within the central nervous system may offer more effective therapies for these disorders. The selective serotonin reuptake inhibitors are commonly used in clinical practice, but more rigorous, controlled studies are needed to determine their effects beyond the treatment of psychiatric comorbidity. The newer generation antidepressants may provide additional insight into the pathophysiology of the brain-gut interactions and their relationship to functional bowel disorders, providing new therapeutic interventions.

Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?

The cardiovascular toxicity of older generation of tricyclic antidepressants (e.g. imipramine, desipramine, amitriptyline, clomipramine) and neuroleptics (e.g. haloperidol, droperidol, thioridazine, pimozide) is well established. These drugs inhibit cardiovascular Na(+), Ca(2+) and K(+) channels often leading to life-threatening arrhythmia. To overcome the toxicity of old generation of antidepressants and antipsychotics, selective serotonin reuptake inhibitor antidepressants (SSRIs: fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, venlafaxin) and several new antipsychotics (e.g. clozapine, olanzapine, risperidone, sertindole, aripiprazole, ziprasidone, quetiapine) were introduced during the past decade. Although these new compounds are not more effective in treating psychiatric disorders than older medications, they gained incredible popularity since they have been reported to have fewer and more benign side effect profile (including cardiovascular) than predecessors. Surprisingly, an increasing number of case reports have demonstrated that the use of SSRIs and new antipsychotics (e.g. clozapine, olanzapine, risperidone, sertindole, aripiprazole, ziprasidone, quetiapine) is associated with cases of arrhythmias, prolonged QTc interval on electrocardiogram (ECG) and orthostatic hypotension in patients lacking cardiovascular disorders, raising new concerns about the putative cardiovascular safety of these compounds. In agreement with these clinical reports these new compounds indeed show marked cardiovascular depressant effects in different mammalian and human cardiovascular preparations by inhibiting cardiac and vascular Na(+), Ca(2+) and K(+) channels. Taken together, these results suggest that the new generation of antidepressants and antipsychotics also have clinically important cardiac as well as vascular effects. Clinicians should be more vigilant about these potential adverse reactions and ECG control may be suggested during therapy, especially in patients with cardiovascular disorders. The primary goal of this review is to shed light on the recently observed clinically important cardiovascular effects of new antidepressants and antipsychotics and discuss the mechanism beyond this phenomenon.

Mirtazepine: heir apparent to amitriptyline?

"What's new in therapeutics?" will examine and evaluate drugs that may have a place in hospice, palliative, and long-term care. Mirtazepine will be examined and evaluated. Mirtazepine is a potential alternative anti-depressant with multiple additional benefits. It is an atypical anti-depressant, which has both noradrenergic and specific serotonergic receptor antagonism (NaSSa), and a unique pharmacological profile. Mirtazepine appears to be a "designer drug" for palliative medicine with a number of benefits, but cost may be a drawback.

[The role of serotonergic system in the mechanism of action of antidepressant agents]. / Rola ukladu serotoninergicznego w mechanizmie dzialania leków przeciwdepresyjnych.

Thirty eight years after the successful clinical introduction of antidepressant agents, there has been an important progress in the knowledge and changes in thinking about the role of central serotonergic system in depression and in the mechanism of their therapeutic efficacy. Although it is not clear whether an increase or decrease in serotoninergic function is more important in antidepressant action of agents, there is increasing evidence that almost all antidepressant drugs can induce changes in the sensitivity of somotodendritic 5-HT1A autoreceptors and postsynaptic 5-HT2 receptors in spite of very different pharmacological profiles after a single administration. The question arises as to the causal nature of the relationship between these effects and beneficial clinical action. Further studies are still required to dispel these doubts.

Antidepressant drug selection: criteria and options.

The dilemma of developing new medications rationally--as opposed to discovering them through serendipity--is to create an optimal balance between the number of mechanisms of action needed for the widest spectrum of antidepressant activity while maximizing safety and tolerability. Newer antidepressants, such as serotonin selective reuptake inhibitors (SSRIs) and venlafaxine, have a wider therapeutic index than the older tricyclic antidepressants. Fewer types of adverse effects and a reduction in the potential for pharmacodynamic interactions are the distinct benefits of all the newer targeted antidepressants, such as venlafaxine, SSRIs, and bupropion, in comparison with older drugs. However, there are important differences among the newer antidepressants in terms of effects of P450 enzymes, dose-response curves for antidepressant response and adverse effects, and dosing schedules. One of the main benefits of having a wide array of options is the evidence that there may be different forms of the illness, which respond to different mechanisms of action. More research is needed to test this concept and to develop predictors of differential responsiveness.

[Plasmatic concentrations of fluoxetine, pharmacokinetics, therapeutic response and side effects]. / Niveles plasmáticos de fluoxetina: farmacocinética, respuesta terapeútica y efectos secundarios.

The kinetics of fluoxetine and possible relations between the drug's plasmatic concentration and therapeutic response and side effects were evaluated in a sample of 66 depressive patients, 26 men and 40 women, average age 46.6 years (SD = 14.1), diagnosed according to DSM-III criteria and evaluated using the Hamilton scale for depression (17-item HRSD). We found no difference between plasmatic concentration of fluoxetine in weeks 3 and 6 of treatment, nor in the sum of drug plus active principle in weeks 3 and 6. There was no significant linear correlation between plasmatic concentrations of fluoxetine, norfluoxetine, or the sum of both in weeks 3 and 6 and score on the Hamilton scale in week 6. By means of serial Chi-score calculation we found a "minimum plasmatic concentration" of about 30 ng/ml below which there was less therapeutic response.

[Atypical tricyclic neuroleptics for treatment of schizophrenia. Clothiapine and clozapine]. / Neurolettici triciclici atipici nella schizofrenia. Clotiapina e clozapina.

The main objective of the pharmacotherapy of schizophrenia has been, and still is, to obtain optimal therapeutic efficacy, which is seconded by the aim to restrict as far as possible the sometimes severe collateral effects which are acknowledged as being the major drawback to the regular use of neuroleptic agents. Tight from the start, some "atypical neuroleptics" were identified as being of interest for this reason; these included Clothiapine and Clozapine, a more recently discovered drug which is not yet commercially available in Italy. Both of these neuroleptics have been found to offer extremely interesting advantages. The authors now report data referring to the clinical use of these drugs during 1989-1990 in addition to those published in the literature on this subject.

[Integrated therapy in panic attack disorders]. / Terapia integrata nel disturbo da attacchi di panico.

For the past years or so, studies on panic attack disorders (PAD) have accounted for a large proportion of psychiatric research. In spite of the attempts to clarify the etiopathogenesis of PAD, its characteristic psychopathological aspects and the evolutionary stages of its development, its nosographic status is still controversial (despite its inclusion in DSM III-R) and the same is true of the therapeutical approach. Using these observation as their starting point, the authors have divided the present paper into four parts. In the first they attempt to classify PAD in nosographical terms, whereas the second reviews all pharmacological therapies put forward over the past ten years. The third part consists of a short summary of the most widely used psychotherapeutic approaches, and in the last the authors suggest a model of integrated PAD therapy which is still being clinically experimented. The practice of associating pharmacological therapy with a psychotherapeutic approach has certainly been widely used for some time, but the authors underline that the two methods are only fully integrated in the presence of a therapeutic project resulting in a treatment protocol with controls during the course and at the end of treatment. In this context, the psychodiagnostic stage before therapy is particularly important since it provides as precise as possible a picture of the subject's basic personality and psychopathological state. These factors can lead to a wide varation in the choice of drug therapy, and even jeopardise therapeutic success. On the other hand, an exclusively psychotherapeutic approach to PAD does not rule out the onset of recurrent episodes during treatment.(ABSTRACT TRUNCATED AT 250 WORDS)