Newer antidepressants. Beyond selective serotonin reuptake inhibitor antidepressants

This article outlines the use of alternative agents to TCAs and SSRIs. Features of the more commonly used alternative antidepressant agents are outlined. In addition, antidepressant agents that are currently either under development or used in other countries are indicated for completeness because it seems likely that many of these will be introduced in the United States within the next few years. Many of these agents will be used by pediatricians and child psychiatrists for treatment of depression in children, and although much further research is needed, the future for alternative antidepressants and augmenting strategies is extremely promising.     

Serotonin 5-HT1A autoreceptor blockade potentiates the ability of the 5-HT reuptake inhibitor citalopram to increase nerve terminal output of 5-HT in vivo: a microdialysis study

The present study addressed the possibility that disinhibition of serotonin (5-HT) autoreceptor-mediated negative feedback might potentiate the elevation of nerve terminal 5-HT output induced by selective 5-HT reuptake blockade. To this end, rats were given citalopram and the 5-HT autoreceptor-blocking agents (S)-UH-301 (5-HT1A) and (-)-penbutolol (5-HT1A/1B), and the effect on extracellular 5-HT in the ventral hippocampus was monitored by means of in vivo microdialysis. Citalopram (5 mg/kg, s.c.) approximately doubled the 5-HT output, a response that was markedly augmented by (S)-UH-301 (3 mg/kg, s.c.) and (-)-penbutolol (8 mg/kg, s.c.) and by combined treatment with (S)-UH-301 (3 mg/kg, s.c.) plus (-)-penbutolol (1 microM; via the dialysis perfusion medium), but not by (-)-penbutolol (1 microM) alone. These findings provide evidence that 5-HT, in particular 5-HT1A, autoreceptor-mediated negative feedback mechanisms are pivotal in determining the nerve terminal 5-HT output level after 5-HT reuptake inhibition. These findings have important implications for the interplay between different processes controlling 5-HT transmission in vivo and might possibly offer a lead toward novel, therapeutically exploitable principles.     

Selective serotonin reuptake inhibitor discontinuation syndrome: Understanding, recognition, and management for psychologists.

Psychologists increasingly provide psychotherapeutic services to patients receiving concomitant pharmacotherapy. Ongoing experience with the relatively new selective serotonin reuptake inhibitors and other atypical antidepressants has revealed a discontinuation syndrome that emerges following abrupt or tapered withdrawal from these agents. The syndrome has both somatic and psychological characteristics, which tend to be mild and transient but can also be more distressing and become temporarily debilitating. Psychologists need to be aware of the potential for these events, as they are in an optimal position to collaborate with physicians and other prescribing clinicians to prevent or manage this syndrome. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Review of cardiovascular effects of fluoxetine, a selective serotonin reuptake inhibitor, compared to tricyclic antidepressants

The objective of this study is to find out which mathematical model best explains the temporal fluctuations of the axial blood flow velocity waveforms in the basal arteries of the brain. Blood flow velocity time series were sampled by transcranial Doppler (TCD) examination of the middle cerebral arteries in 10 healthy volunteers. A recently developed mathematical test (surrogate data analysis) was used to examine whether the spectral Doppler maximum waveform consistent with some prespecified model (null hypothesis). We tested four different null hypothesis. 1. Uncorrelated white noise. 2. Linearly filtered noise. 3. Linearly filtered noise with a static nonlinear amplitude transformation. 4. Noisy nonlinear limit cycle. All null hypotheses except the last one could be rejected. We conclude that the TCD waveforms are best described as nonlinear limit cycle with some percentage of noise, either dynamical and/or observational, which is uncorrelated from one single oscillation to the next. These results are a strong argument to perform nonlinear analysis in future TCD studies in order to obtain a better understanding of the cerebral hemodynamics.     

The selective norepinephrine reuptake inhibitor, LY368975, reduces food consumption in animal models of feeding

PURPOSE: The present study evaluated the cytostatic and apoptotic effects of a 24-hr paclitaxel treatment in ovarian tumors. METHODS: Three-dimensional histocultures of surgical specimens from patients (n = 17) were used. The cytostatic effect was measured by inhibition of 96-hr cumulative DNA precursor incorporation and induction of apoptosis was determined by morphological changes. RESULTS: Paclitaxel produced partial inhibition of DNA precursor incorporation in about 40% of tumors (maximum inhibition of approximately 30%) and induced apoptosis in about 90% of tumors (maximum apoptotic index of approximately 15%). In responsive tumors, maximum cytostatic and apoptotic effects were achieved at < or = 1 microM with no further enhancement by increasing the drug concentration to 10 microM. In individual tumors, the apoptotic effect inversely correlated with cytostatic effect (r2 = 0.27, p = 0.031), and the maximal apoptotic index correlated with the LI for the untreated controls (r2 = 0.38, p < 0.01). More than 95% of apoptotic cells after paclitaxel treatment were labeled with DNA precursor. The incomplete cytostatic and apoptotic effects of paclitaxel and the link between DNA synthesis and apoptosis in ovarian tumors are similar to our previous findings in other human solid tumors. CONCLUSIONS: These findings suggest that (a) apoptosis is the major paclitaxel effect in advanced ovarian tumors, (b) tumor sensitivity to drug-induced cytostatic effect is opposite to sensitivity to apoptotic effect, (c) paclitaxel-induced apoptosis increases with increased cell proliferation and is completed after DNA synthesis, and (d) further increasing the dose to elevate plasma concentration beyond 1 microM may not improve treatment outcome.     

Successful outcome in a patient with chemical sensitivity. Treatment with psychological desensitization and selective serotonin reuptake inhibitor

A 49-year-old male was diagnosed as having primary aldosteronism at age 39, and he was treated with antihypertensive drugs. In 1995, a computed tomogram revealed a mass in the right adrenal gland. Radiological examinations and endocrinological data revealed the presence of a pheochromocytoma in the right and an adrenocortical tumor in the left adrenal gland. Right adrenalectomy and left partial adrenalectomy were performed. Histologically, the right adrenal mass was compatible with pheochromocytoma, and the left adrenal mass was an adrenocortical adenoma. Endocrinological data as well as blood pressure returned to normal after operation.     

Progressive resistance to a selective serotonin reuptake inhibitor but not to cognitive therapy in the treatment of major depression.

Recent research suggests that there may be a reduction in therapeutic response after multiple administrations of antidepressant drug (AD) therapy in patients with major depressive disorder. This study assessed the response to AD therapy and cognitive therapy (CT) of patients with a history of prior AD exposures. A sample of 240 patients with moderate-to-severe major depressive disorder entered a randomized controlled trial comparing pharmacotherapy with paroxetine to CT. Treatment was administered for 16 weeks. History of prior AD exposure was assessed with structured interviews, self-report, and medical records. Analyses were conducted using hierarchical linear models on the intent-to-treat sample. After controlling for various demographic and clinical factors, more prior AD exposures predicted poor response to paroxetine therapy but not to CT, as measured by the Hamilton Rating Scale for Depression (Hamilton, 1960; Williams, 1988). Whereas CT outcome was not significantly related to the number of prior AD exposures, a higher number of prior AD exposures was significantly associated with a lower response to paroxetine. If these findings are replicated in methodologically rigorous studies of paroxetine and other antidepressants, CT should be recommended, in preference to AD, for patients with multiple prior AD exposures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Digital infarction in a patient with Raynaud''s phenomenon associated with treatment with a specific serotonin reuptake inhibitor. A case report

Palatopharyngeal injuries due to impaction of rigid objects held in the mouth are common. Most are essentially innocuous injuries requiring no specific treatment. However, there is the potential for perforation of the pharyngeal wall with the subsequent development of serious infection such as retropharyngeal abscess or mediastinitis. This possibility is more likely to be suspected in the presence of a visible laceration or puncture wound at the site of impact in the mouth or pharynx. We report three cases in which occult pharyngeal perforation occurred without any clinical signs of breech of the pharyngeal wall. In all cases a lateral soft tissue neck X-ray was diagnostic of perforation, showing the presence of retropharyngeal air. We, therefore, advocate the routine performance of soft tissue neck X-rays in all patients who present with a history of falling on a rigid object held in the mouth.     

Matrix metalloproteinase and matrix metalloproteinase inhibitor expression in endometrial stromal cells during progestin-initiated decidualization and menstruation-related progestin withdrawal

Estradiol (E) primes human endometrial stromal cells (HESCs) for the decidualizing effects of progesterone in vivo and in vitro. Matrix metalloproteinase (MMP) expression was evaluated in confluent HESCs incubated in control medium, and in medium supplemented with either E, or the synthetic progestin medroxyprogesterone acetate (P), or E + P. Measurements with a specific ELISA indicated that basal pro-MMP-1 output was unaffected by E, whereas E + P, which induces the expression of several decidualization-related markers, produced a time-dependent inhibition in HESC-secreted levels of pro-MMP-1. Consistent with progestin inhibition of MMP-1 protein expression in the HESCs, P but not E, reduced steady state levels of MMP-1 messenger RNA (mRNA) as determined by Northern analysis. By contrast, mRNA levels for MMP-2 and the MMP inhibitor TIMP-1 were not altered by either P or E. Steroid withdrawal studies indicated that after MMP-1 expression was suppressed by incubation of the HESCs with E + P, 4 days of exposure to the antiprogestin RU 486 (mifepristone) significantly up-regulated MMP-1 levels in the conditioned medium by severalfold compared with cultures maintained in E + P. The change to steroid-free control medium required a more prolonged period of withdrawal to attain up regulatory effects that were comparable with those evoked by RU 486. The ELISA measurements were validated by immunoblot analysis with a specific MMP-1 antibody, which showed corresponding changes in a band at the expected mobility of about 50 kDa. Moreover, Northern analysis revealed parallel changes in MMP-1 mRNA levels, whereas neither MMP-2 nor TIMP-1 mRNA levels were modulated by adding or withdrawing steroids. The contrast between regulated MMP-1 expression and constitutive MMP-2 expression observed in the cultured HESCs is consistent with the demonstrated presence on the MMP-1 promoter of regulatory elements such as AP-1 and PEA-3 that are absent from the MMP-2 promoter. Extrapolation of these in vitro changes in HESCs to in vivo endometrial events suggests that: 1) inhibition of MMP-1 expression by E and progesterone would stabilize the perivascular endometrial ECM to prevent local hemorrhage during endovascular invasion by the implanting trophoblast; 2) enhanced expression of MMP-1 evoked by steroid withdrawal would mediate endometrial ECM degradation leading to sloughing of the functional layer during menstruation.     

Cost effectiveness study of a year follow-up of selective serotonin reuptake inhibitor (SSRI) and augmentor combination compared with SSRI and placebo

We describe a method for evaluating the value of increased cost of pharmacological augmentation that, taken for 6 weeks, accelerates the action of an antidepressant. We test the hypothesis that, if onset of action is taken into account, any added direct costs of the augmenting agent are offset by longer term cost effectiveness. Data to illustrate the method were based on a double-blind randomized placebo controlled study, in which 80 patients originally took part. Patients received the selective serotonin reuptake inhibitor (SSRI) antidepressant paroxetine and an augmenting agent (pindolol) or placebo. After 6 weeks, patients were offered SSRI alone on an open label basis for up to 6 months. At that point they were discharged to their general practitioner or local psychiatric services and subsequently assessed by us at one year. We have used techniques of decision analysis, cost effectiveness and cost benefit and have included a sensitivity analysis. The direct costs over one year of SSRI and augmenting agent, if taking the acceleration effect into account, represented greater cost effectiveness than the SSRI antidepressant alone. The cost effectiveness analysis was positive in both cases. We conclude that the direct costs of treatment are higher than those of previous calculated with SSRIs; but the rate of onset must be taken into account. The application of the model appears valid and useful, and may be used as part of the evaluation of other augmentation regimes.     

Alcoholic withdrawal delirium

The actual progress of medical studies, reach to 1% in comparison with former data 20% a number of death in delirium tremens. The aim of this study is the presentation the symptoms of alcohol psychosis, as well as of various methods of it's cure. To choose of right therapy is sometimes very difficult for the physician. In this work one tries to explain pathogenesis of delirium tremens. Author's doctors of first contact in achieving right diagnosis and therapy.