Abrupt Withdrawal Research Articles

Why does milnacipran produce so few discontinuation syndromes following abrupt withdrawal?

Several selective serotonin reuptake inhibitors (SSRI), especially paroxetine, have been reported to produce a number of post-treatment emergent adverse events following abrupt withdrawal (Coupland et al 1996; Haddad 1997). More recently a SSRI-induced neonatal withdrawal syndrome has been described (Sanz et al 2005) in infants born of mothers treated with SSRI during pregnancy. In both of these situations, paroxetine has been associated with the greatest incidence (Warner et al 2006; Sanz et al 2005). Other SSRIs and the selective serotonin and noradrenaline reuptake inhibitor (SNRI) venlafaxine can, however also cause a withdrawal syndrome in patients (Trenque et al 2002). In contrast, milnacipran, another SNRI, has been reported to present a lower risk of withdrawal-induced adverse events (Vandel et al 2004). Furthermore the spectrum of the symptoms was different from that produced by paroxetine. In our clinic, a discontinuation syndrome is sometimes seen when SSRIs or SNRIs are discontinued suddenly, or when doses are missed or forgotten. In a total cohort of 2675 depressed patients, we identified 124 cases of antidepressant withdrawal syndrome. Sixty-three of the cases resulted from withdrawal from fluvoxamine (from a total of 1306 treated patients), 55 were withdrawn from paroxetine (from a total of 453 treated patients), while 6 were withdrawn from milnacipran (from a total of 916 treated patients). With paroxetine and fluvoxamine, respectively, the incidence of discontinuation syndrome was 18.4 times greater and 7.3 times greater than that found with milnacipran (Table 1). These differences were highly significant as determined by the χ2 test. These results are qualitatively similar to those obtained in a double-blind comparative study of milnacipran and paroxetine by Vandel et al (2004), who found an incidence of discontinuation syndrome of 13% with milnacipran and 32% with paroxetine following withdrawal after 6 weeks of treatment. Table1 Number and ratios of discontinuation syndrome with SSRIs and SNRI in our clinic Paroxetine has systematically been found to have the highest incidence of discontinuation syndrome (Warner et al 2006) while fluvoxamine has an incidence 10-fold lower and fluoxetine 100-fold lower (Westenberg and Sandner 2006). Paroxetine is the most potent inhibitor of the serotonin transporter (Sanchez and Hyttel 1999) and this potency may be a significant factor in the frequency of discontinuation syndromes for paroxetine in comparison with fluvoxamine (Westenberg and Sandner 2006) and milnacipran (Moret et al 1985). Furthermore, paroxetine is unique among the SSRI because its relatively high affinity for muscarinic receptors is similar to that of imipramine (Schatzberg et al 1997; Sanchez and Hyttel 1999). A cholinergic rebound, as observed on withdrawal of tricyclic antidepressants (Dilsaver et al 1987), could also partly explain the discontinuation syndrome paroxetine. Neither fluvoxamine nor milnacipran have any significant affinity for the muscarinic receptor (Moret et al 1985; Sanchez and Hyttel 1999). Pharmacokinetics are thought to play an important role in the incidence of withdrawal effect, with compounds with shorter half-lives having the greatest incidence of withdrawal effects. The apparent correlation between the occurrence of SSRI discontinuation syndrome and shorter drug half-lives has been highlighted (Schatzberg et al 1997). The half-life of paroxetine (21 h) may explain the relatively high incidence of discontinuation syndromes compared with fluoxetine which has a long half-life (parent compound 1–6 days, active metabolite 7–9 days). Pharmacokinetic factors, however, do not explain the low incidence of withdrawal effects with milnacipran, since the half-life of the SNRI (8 h) is shorter than that of paroxetine (Puozzo et al 1998). It is possible that low incidence of withdrawal effects with milnacipran may be related to its dual action on the reuptake of noradrenaline and serotonin compared with the selective effect of SSRI such as paroxetine on the reuptake of serotonin. It seems unlikely, however, that a simple action on the noradrenaline transporter is sufficient to explain the situation. Firstly, paroxetine is the SSRI with the highest affinity for the noradrenaline transporter (Sanchez and Hyttel 1999) and, secondly, the SNRI venlafaxine has an incidence almost as high as paroxetine (Trenque et al 2002). Although venlafaxine is considered to be a SNRI, it is, in fact, a preferential serotonin reuptake inhibitor and produces clinically relevant inhibition of noradrenaline reuptake only at high doses where serotonin reuptake is very extensively inhibited (Harvey et al 2000). A unique property of milnacipran which may be relevant is the fact that it inhibits both noradrenaline and serotonin reuptake with similar potency (Moret and Briley 1997). A recent study of changes in long-term potentiation following repeated treatment with milnacipran (Tachibana et al 2006) has shown that interactions between noradrenergic and serotonergic mechanisms play an important role in the modulation of synaptic plasticity. It is thus possible that the balance between serotonergic and noradrenergic neurotransmission may be essential in determining the nature and extent of withdrawal-related symptoms. Further preclinical and clinical studies are required to test this hypothesis.

Effect of Neurosteroid Withdrawal on Spontaneous Recurrent Seizures in a Rat Model of Catamenial Epilepsy

Women with epilepsy often report an increase in seizures at the time of menstruation, a condition referred to as catamenial epilepsy. Perimenstrual seizure exacerbation has long been known to be associated with an abrupt withdrawal of progesterone. The progesterone’s antiseizure effect is due in part to its conversion to the “neurosteroid” allopregnanolone. However, there is no specific animal model of catamenial epilepsy. In this study, we sought to develop a rat model of catamenial seizure exacerbation based on the premise that allopregnanolone withdrawal leads to the exacerbation of spontaneous seizures in epileptic state. Chronic epilepsy was induced in rats by treatment with pilocarpine. Rats were monitored for spontaneous seizures during 2–6 months post pilocarpine. EEG was recorded from hippocampus and cortex. Pilocarpine treatment was associated spontaneous seizures after latency of 60 days post pilocarpine. The average seizure frequency was 15 seizures per week. At 5 months post pilocarpine, majority of rats exhibited bilateral neurodegeneration and a robust aberrant mossy fiber sprouting. To model catamenial seizure exacerbation, epileptic rats were subjected to repeated neurosteroid withdrawal by a pseudopregnancy-finasteride paradigm. Neurosteroid withdrawal showed a tendency of increased seizure frequency, including exacerbation of EEG discharges. Thus, this neurosteroid withdrawal paradigm in epileptic rats may provide a suitable animal model of catamenial seizure exacerbation for use in testing novel agents. ∗∗ Supported by NIH/NINDS grant NS052158 ∗∗

Can medication overuse headache be treated by abrupt withdrawal of the overused agent?

Can medication overuse headache be treated by abrupt withdrawal of the overused agent?

An in Vitro Model of Morphine Withdrawal Manifests the Enhancing Effect on Human Immunodeficiency Virus Infection of Human T Lymphocytes through the Induction of Substance P

Opioid withdrawal is a crucial and recurring event during the course of opioid abuse that has a negative impact on the immune system. In this study, we investigated whether abrupt withdrawal (AW) or precipitated withdrawal (PW) potentiates human immunodeficiency virus (HIV) infection of human T lymphocytes. AW and PW enhanced HIV infection of peripheral blood lymphocytes and T-cell lines (Jurkat and CEMX174). In addition, both AW and PW induced HIV replication in a latently HIV-infected human T-cell line (J1.1). The enhancing effect of AW and PW was associated with the induction of neuropeptide substance P in both peripheral blood lymphocytes and the T-cell lines. The substance P receptor antagonist, CP-96,345, not only blocked AW- or PW-induced endogenous substance P expression but also abrogated AW- or PW-induced HIV replication in T cells. These findings provide a cellular mechanism that supports the notion that opioids have a co-factor role in promoting HIV infection of the immune cells.

Mycophenolate Mofetil in Children with Frequently Relapsing Nephrotic Syndrome

Children with frequently relapsing nephrotic syndrome (FRNS) often develop adverse effects from prednisone. Attempts to induce long-term remission in such patients have had varying levels of success. In this multicenter, prospective, open-label study, 14 centers enrolled 33 patients with FRNS, all of whom were in remission at the time of entry. Six of the patients were steroid dependent. The patients received mycophenolate mofetil (MMF) 600 mg/m(2) twice daily (maximum 1 g twice daily) for 6 mo. A tapering dosage of alternate-day prednisone was given to each patient during the first 16 wk of MMF therapy. Patients were monitored for relapses of NS during and after MMF therapy. Treatment failure was defined as a relapse of NS. The patients had the following features at study entry: Age 6.8 +/- 2.7 yr (range 2 to 15 yr); 56% male, 44% female; and 50% white; 25% black, and 25% other. Estimated GFR at entry was 138 +/- 42 ml/min per 1.73 m(2). Twenty-four (75%) of 32 patients stayed in remission throughout the 6 mo of MMF therapy. The relapse rate in these patients improved from one episode every 2 mo before MMF to one every 14.7 mo after MMF. Eight patients stayed in remission during the post-MMF period, for periods of 18 to 30 mo, whereas 16 relapsed after stopping MMF. Eight (25%) of 32 patients relapsed while taking MMF. It is concluded that MMF is effective for maintaining remission in patients who have FRNS and receive treatment for at least 6 mo and is associated with a low incidence of adverse events.

Sleep disorders in psychiatry

Sleep is an active state that is critical for our physical, mental, and emotional well-being. Sleep is also important for optimal cognitive functioning, and sleep disruption results in functional impairment. Insomnia is the most common sleep disorder in psychiatry. At any given time, 50% of adults are affected with 1 or more sleep problems such as difficulty in falling or staying asleep, in staying awake, or in adhering to a consistent sleep/wake schedule. Narcolepsy affects as many individuals as does multiple sclerosis or Parkinson disease. Sleep problems are especially prevalent in schizophrenia, depression, and other mental illnesses, and every year, sleep disorders, sleep deprivation, and sleepiness add billions to the national health care bill in industrialized countries. Although psychiatrists often treat patients with insomnia secondary to depression, most patients discuss their insomnia with general care physicians, making it important to provide this group with clear guidelines for the diagnosis and management of insomnia. Once the specific medical, behavioral, or psychiatric causes of the sleep problem have been identified, appropriate treatment can be undertaken. Chronic insomnia has multiple causes arising from medical disorders, psychiatric disorders, primary sleep disorders, circadian rhythm disorders, social or therapeutic use of drugs, or maladaptive behaviors. The emerging concepts of sleep neurophysiology are consistent with the cholinergic-aminergic imbalance hypothesis of mood disorders, which proposes that depression is associated with an increased ratio of central cholinergic to aminergic neurotransmission. The characteristic sleep abnormalities of depression may reflect a relative predominance of cholinergic activity. Antidepressant medications presumably reduce rapid eye movement (REM) sleep either by their anticholinergic properties or by enhancing aminergic neurotransmission. Intense and prolonged dreams often accompany abrupt withdrawal from antidepressant drugs, a reflection of an REM rebound after drug-induced REM deprivation. The postulated link between sleep and psychiatric disorders has been reinforced by the findings of modern neurobiology.

Preoperative cardiac drug administration in general surgical patients: a completed audit

The aim of this study was to audit the preoperative administration of regular cardiac medication in general surgical patients and to determine if this can be improved with simple ward-based education. The notes and drug charts of 102 general surgical adult inpatients undergoing elective operations were analysed prospectively. It was noted whether the patient was on regular morning cardiac medication, whether this was given and, if not, whether a reason was recorded on the drug chart. An information sheet and brief verbal reinforcement was given to nursing staff and junior doctors and the review repeated in 111 patients. There was no significant difference in the number of patients on regular cardiac medication between the two review groups; 42% patients had one or more drugs omitted in the initial review. After education this reduced significantly to 20% (p = 0.023). When omissions on medical instruction were excluded, this became highly significant (p = 0.0029). There was also a significant decrease in the number of times 'nil by mouth' was stated as the reason for omission. As a general principle, all regular cardiac medication should be given preoperatively even when nil by mouth as there is evidence that abrupt withdrawal can have serious consequences. This audit demonstrates that with simple education, the proportion of regular cardiac drugs administered preoperatively can be significantly increased.

Morphine Withdrawal Lowers Host Defense to Enteric Bacteria: Spontaneous Sepsis and Increased Sensitivity to Oral Salmonella enterica Serovar Typhimurium Infection

Understanding the consequences of drug withdrawal on immune function and host defense to infection is important. We, and others, previously demonstrated that morphine withdrawal results in immunosuppression and sensitizes to lipopolysaccharide-induced septic shock. In the present study, the effect of morphine withdrawal on spontaneous sepsis and on oral infection with Salmonella enterica serovar Typhimurium was examined. Mice were chronically exposed to morphine for 96 h by implantation of a slow-release morphine pellet. Abrupt withdrawal was induced by removal of the pellet. In the sepsis model, bacterial colonization was examined and bacterial species were identified by necropsy of various tissues. It was found that at 48 h postwithdrawal, morphine-treated mice had enteric bacteria that were detected in the Peyer's patches (4/5), mesenteric lymph nodes (4/5), spleens (4/10), livers (6/10), and peritoneal cavities (8/10). In placebo pellet-withdrawn mice, only 2/40 cultures were positive. The most frequently detected organisms in tissues of morphine-withdrawn mice were Enterococcus faecium followed by Klebsiella pneumoniae. Both organisms are part of the normal gastrointestinal flora. In the infection model, mice were orally inoculated with S. enterica 24 h post-initiation of abrupt withdrawal from morphine. Withdrawal significantly decreased the mean survival time and significantly increased the Salmonella burden in various tissues of infected mice compared to placebo-withdrawn animals. Elevated levels of the proinflammatory cytokines were observed in spleens of morphine-withdrawn mice, compared to placebo-withdrawn mice. These findings demonstrate that morphine withdrawal sensitizes to oral infection with a bacterial pathogen and predisposes mice to bacterial sepsis.

“Broken Heart Syndrome” After Separation (From OxyContin)

We describe a 61-year-old woman with "broken heart syndrome" (Takotsubo-like cardiomyopathy) after abrupt postsurgical withdrawal of OxyContin. Her medical history was remarkable for long-term opiold dependence associated with the treatment of multi-Joint degenerative osteoarthritis. The patient presented to the emergency department 1 day after discharge from the hospital following total knee arthroplasty revision with acute-onset dyspnea and mild chest pain. She had precordial ST-segment elevation characteristic of acute myocardial infarction and elevated cardiac biomarkers. Emergency coronary angiography revealed no major coronary atherosclerosis. However, the left ventricular ejection fraction was severely decreased (26%), and new regional wall motion abnormalities typical of broken heart syndrome were noted. In addition to resuming her opioid therapy, she was treated supportively with bilevel positive airway pressure, diuretic therapy, morphine, aspirin, metoprolol, enalaprilat, intravenous heparin, nitroglycerin infusion, and dopamine infusion. Ventricular systolic function recovered completely by the fourth hospital day. To our knowledge, broken heart syndrome after opioid withdrawal has not been reported previously in an adult. Our case illustrates the importance of continuing adequate opiate therapy perioperatively in the increasing number of opioid-dependent patients to prevent potentially life-threatening complications such as broken heart syndrome.

The 2006 International Stroke Conference Orlando, Florida February 15-18, 2006

The 2006 International Stroke Conference Orlando, Florida February 15-18, 2006

Ranolazine for the Treatment of Chronic Angina and Potential Use in Other Cardiovascular Conditions

Chronic angina, a condition that impairs quality of life and is associated with decreased life expectancy, affects &6.4 million Americans.1 Current therapies that reduce angina frequency and nitrate consumption and increase the threshold at which demand-induced myocardial ischemic symptoms become evident include drugs (nitrates, β-blockers, calcium antagonists), exercise conditioning, enhanced external counterpulsation, and coronary revascularization.1–3 Several new investigational drugs are being tested for the treatment of chronic angina.4–9 This review will focus on sustained-release ranolazine, a drug that reduces angina symptoms, with a mechanism of action different from that of currently available pharmacological therapies.8–29 Ranolazine was approved on January 27, 2006, in the United States for use in patients with chronic angina who continue to be symptomatic on β-blockers, calcium antagonists, or nitrates. Ranolazine ([(+) N -(2,6-dimethylphenyl)-4(2-hydroxy-3-(2-methoxyphenoxy)-propyl)-1-piperazine acetamide dihydrochloride]) is an active piperazine derivative that was patented in 1986 and is available in an oral and intravenous form (Figure 1). The immediate-release ranolazine (not in current use) had an average terminal elimination half-life ranging from 1.4 to 1.9 hours and a 10-fold peak/trough difference with dosing of 240 to 400 mg 3 times per day.19 Early studies with immediate-release ranolazine provided evidence of antiischemic/antianginal properties in patients with chronic angina without clinically significant changes in heart rate or blood pressure and are reviewed elsewhere.20–24 Unless otherwise stated, the remainder of this review refers to sustained-release ranolazine. Figure 1. Chemical structure and metabolism of ranolazine. Reprinted with permission from J Clin Pharmacol . 2005;45:422–433.17 Ranolazine (Ranexa; CV Therapeutics Inc, Palo Alto, Calif) is manufactured in a sustained-release form that has a prolonged absorption phase with maximal plasma concentrations (Cmax) typically seen 4 to 6 hours after administration. The average terminal elimination half-life is &7 hours after multiple dosing to steady state, and the …

Outcome of Medication Overuse Headache after Abrupt in-Patient withdrawal

One hundred and one patients suffering from chronic daily headache (CDH) and medication overuse were treated, in an in-patient setting, with abrupt discontinuation of the medication overused, intravenous hydrating, and intravenous administration of benzodiazepines and ademetionine. The mean time to CDH resolution was 8.8 days. The in-patient withdrawal protocol used was effective, safe and well tolerated. There was a trend for a shorter time to CDH resolution in patients who overused triptans (P=0.062). There was no correlation between time to CDH resolution and either the type of initial primary headache or duration of medication abuse, whereas time to CDH resolution was related to daily drug intake (P=0.01). In multiple regression analysis, daily drug intake, age and type of medication overused were independent predictors of time to CDH resolution. At 3-months' follow-up, no patient had relapsed and was again overusing symptomatic medications.

Fear state induced by ethanol withdrawal may be due to the sensitization of the neural substrates of aversion in the dPAG

The neural substrate underlying the aversive effects induced by ethanol abstinence is still unclear. One candidate for such effects is the dorsal periaqueductal gray (dPAG), a core structure of the brain aversion system. The main aim of this study is to examine the role of the dPAG as a possible locus of the aversive effects following abrupt alcohol withdrawal. To this end, rats were subjected to an oral ethanol self-administration procedure, in which animals were offered 6-8% (v/v) ethanol solution for a period of 21 days followed by an abrupt discontinuation of the treatment on the two subsequent days. Control animals received control dietary fluid for similar periods of time. The effects of ethanol withdrawal were examined in the elevated plus-maze (EPM) (Exp. I), on the prepulse inhibition of startle to loud sounds (Exp. II) and on the freezing and escape responses induced by electrical stimulation of the dPAG (Exp. III). In Experiment III, rats were implanted with an electrode aimed at the dPAG and the number and duration of ultrasonic vocalizations (USVs) were also recorded in the rats that received dPAG stimulation at freezing and escape thresholds. Data obtained showed that ethanol withdrawal elicited significant "anxiety-like" behaviors, as revealed by the decrease in the number of entries into and time spent onto the open arms of the EPM. Startle reflex and prepulse inhibition remained unchanged in withdrawn animals. In addition, discontinuation from the chronic ethanol regimen caused a reduction in the stimulation thresholds for freezing and escape and in the number and duration of USVs. Together, these effects have been interpreted in the frame of a high fear state elicited by activation of the dPAG. These findings are indicative that ethanol withdrawal sensitizes the substrates of fear at the level of this midbrain structure.

Obviation of Opioid Withdrawal Syndrome by Concomitant Administration of Naltrexone in Microgram Doses: Two Psychonautic Bioassays

Two psychonautic bioassays (self-experiments) in stepwise and abrupt cessation of long-term daily oral ingestion habits of 800 mg of codeine phosphate are presented. Concomitant administration of minute doses (about 0.5 meg) of the opioid antagonist naltrexone with each dose of codeine was found in both cases to obviate the expected opioid withdrawal syndrome, resulting in asymptomatic and uneventful transitions from physical opioid dependency states to exogenous opioidfree metabolism. These experiments are analyzed in the context of a conjectured, rapid, iterative reduction and complete elimination of opioid tolerance, once acquired. It was found that coadministration of naltrexone with codeine phosphate obviated the development of both tolerance and physical dependency over several months of four daily oral doses of 200 mg, allowing abrupt (“cold turkey”), asymptomatic and uneventful withdrawal. This points the way to the biochemical substrate of opioid tolerance itself, and shows that this can easily and inexpensively be blocked, even over months of iterative oral administration of substantial doses of opioid analgesics. Finally, it suggests the opioid withdrawal syndrome is directly related to the physiology of opioid tolerance, and can be prevented by blocking tolerance itself. Even when tolerance has been acquired, this can be reduced stepwise over a matter of days, with no symptoms of opioid withdrawal syndrome.

Neuroleptic Malignant Syndrome Related to a Switch to Perospirone and Anticholinergic Withdrawal

Back to table of contents Previous article Next article Letter to the EditorFull AccessNeuroleptic Malignant Syndrome Related to a Switch to Perospirone and Anticholinergic WithdrawalHISASHI TANII, M.D., Ph.D., KOHEI FUJITA, M.D., and YUJI OKAZAKI, M.D., HISASHI TANIISearch for more papers by this author, M.D., Ph.D., KOHEI FUJITASearch for more papers by this author, M.D., and YUJI OKAZAKISearch for more papers by this author, M.D., Mie, JapanPublished Online:1 Mar 2006https://doi.org/10.1176/appi.ajp.163.3.547-bAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor:We report the first case, to our knowledge, of neuroleptic malignant syndrome related to perospirone. The patient’s medication had been switched from olanzapine and an anticholinergic drug approximately 2 weeks previously. When treated with perospirone without anticholinergics, the patient had a fulminant neuroleptic malignant syndrome that was complicated with rhabdomyolysis and acute renal failure.Mr. A, a 43-year-old man, had suffered from paranoid schizophrenia for 27 years. He had been admitted to a psychiatric hospital 11 times between the ages of 21 and 33 because of insomnia, psychomotor agitation, and persecutory delusions. His illness had been maintained with a dose of 9–15 mg/day of bromperidol for more than 20 years. Bromperidol is a butyrophenone neuroleptic that shows a similar pharmacodynamic response as haloperidol. Six weeks before his admission, Mr. A’s medication was switched to risperidone and biperiden, and bromperidol was discontinued because of the drug-induced extrapyramidal symptom of a hand tremor.Three weeks later, risperidone was switched to olanzapine because Mr. A felt that risperidone did not effectively treat his symptoms. After Mr. A had been taking the medication for 3 weeks, olanzapine and biperiden were discontinued, and perospirone, 16 mg/day, was introduced because of psychiatric symptoms, such as auditory hallucinations and diarrhea. On the 12th day of perospirone treatment, Mr. A suddenly became confused and obtunded with severe muscle rigidity. When he was admitted to a psychiatry department, he had a high fever, tachycardia, and severe extrapyramidal symptoms. Laboratory tests showed an elevation of creatine phosphokinase (33,878 IU/liter) and leukocyte levels (30.9×109/liter). A urine analysis showed myoglobinuria. A brain computerized tomography scan showed no remarkable change, and the possibility of infectious disease was excluded.Mr. A had a fulminant neuroleptic malignant syndrome complicated with rhabdomyolysis and acute renal failure. On the third day of admission, he was transferred to an intensive care unit. He received dantrolene treatment and hemodialysis. On the 19th day, the fever disappeared, and his serum creatine phosphokinase level was normal (112 IU/liter). On the 44th day, his muscle rigidity was resolved, and no psychiatric symptoms were observed. He was discharged on the 46th day.This case report shows that neuroleptic malignant syndrome can occur after a switch to perospirone treatment from other antipsychotics and anticholinergic withdrawal. Perospirone is a novel serotonin-dopamine antagonist and also a partial serotonin (5-HT1A) agonist (1). The receptor binding profile and pharmacological property of perospirone resemble those of risperidone, and side effects, such as extrapyramidal symptoms, tend to occur less often with perospirone (2). This patient did not develop neuroleptic malignant syndrome during previous risperidone and olanzapine treatment with anticholinergics. It has been reported that abrupt withdrawal of anticholinergic agents is associated with neuroleptic malignant syndrome (3). Special caution with regard to concomitant drugs is therefore necessary when switching between antipsychotic drugs.

Can Medication-Free Research Ever Be Ethical in Older People With Psychotic Disorders?

Can Medication-Free Research Ever Be Ethical in Older People With Psychotic Disorders?

Section 7: Heart Failure in Patients With Left Ventricular Systolic Dysfunction

Section 7: Heart Failure in Patients With Left Ventricular Systolic Dysfunction

Pain, the DEA, and the Impact on Patients

Dr. Heit provides an excellent summary of the events that constitute the history of the attempt to create balance—curbing diversion while simultaneously protecting access to pain medicines. It is, unfortunately, a sad story. Going from the optimism after producing and disseminating Prescription Pain Medications: Frequently Asked Questions and Answers (FAQ), to the disappointment of the abrupt withdrawal of the same document with subsequent “clarifications” that reflected a significant retreat from the goal of protecting access to pain medicines for people who need them, the story's current ending has many, many victims—people affected by pain. From the perspective of the pain patient, things …

Rebound phenomenon of inflammatory response may be a major mechanism responsible for increased cardiovascular events after abrupt cessation of statin therapy

Inflammation has been recognized as having an important role in the development and progression of atherosclerosis. Statins reduce cardiovascular events mainly by cholesterol lowering. A large number of investigations have demonstrated that administration of statin could modify inflammatory response with a concurrent fall in cardiovascular events. Despite the known benefit of statin therapy, many cardiac patients abruptly discontinue therapy because of financial constraints, forgetfulness, or side effects. More recently, several studies have shown that abrupt cessation of statin therapy during treatment could increase the incidence of cardiac events in patients with atherosclerotic heart disease. However, the mechanisms of the increased incidence of cardiovascular events after abruptly stopping statin therapy are still unknown. A few data suggest that abrupt withdrawal of statin therapy deteriorates endothelial function, result in expression of pro-inflammatory gene involved in the development and progression of atherosclerosis. We hypothesis that rebound phenomenon of inflammatory response may be a major mechanism responsible for increased cardiovascular events after abrupt cessation of statin therapy. Our very recent data showed that abrupt termination of statin therapy resulted in a rapid increased C-reactive protein (CRP) and interleukin-6 (IL-6) levels in patients with hypercholesterolemia. This finding may be of important interest in the connection between inflammatory response and abrupt withdrawal of statin therapy in patients with coronary artery disease.

Vacunas anti-rotavirus: Al fin una realidad

Rotavirus is the most common cause of severe acute diarrhea among children less than 3 years of age. This infection causes 25 million medical visits, 2 million hospitalizations and 440,000 deaths every year worldwide. The development of rotavirus vaccines has followed a long and difficult path seriously hampered by the abrupt withdrawal of Rotashield in 1999 due to its association with intestinal intussusception. After six years of intense research, the world celebrates the licensing of two new rotavirus vaccines, different in formulation and administration schemes albeit clearly safe and not associated with intussusception as demonstrated by large Phase III trials including more than 60,000 children. These vaccines, Rotarix from Glaxo SmithKline Biologicals and Rotateq from Merck Sharp & Dohme, have demonstrated to be highly efficacious against severe rotavirus gastroenteritis caused by the most prevalent serotypes. Prompt incorporation of these new vaccines into the immunization programs of countries, especially those in the poorest areas of the world where these vaccines are most needed, will require joint efforts between governments, vaccine manufacturers, international and non-governmental organizations and foundations.