Severe withdrawal symptoms with fever during paroxetine tapering off]

A 30-year-old man with depression who was treated with paroxetine (Seroxat) developed severe withdrawal symptoms when the medication was gradually diminished and stopped: agitation, irritability, vertigo, lightheadedness and fever up to 40 degrees C. The symptoms disappeared after the medication was reintroduced but recurred after rediscontinuation. When the dosage was diminished very gradually the symptoms were mild. The depression did not recur. Such withdrawal symptoms are most prevalent after discontinuation of paroxetine but can occur after use of all selective serotonin reuptake inhibitors. The withdrawal syndrome includes both physical and psychiatric symptoms and needs to be distinguished from a relapse of the psychiatric disorder. Good information and gradual discontinuation of the antidepressant after long-term use are adequate measures to prevent severe withdrawal symptoms.     

Increased perioperative blood loss during treatment with paroxetine

A 63-year-old man who took paroxetine for depression developed massive peroperative haemorrhage during a pancreaticoduodenectomy as a result of paroxetine-induced thrombocytopathy. He lost 4 litres of blood. After administration of 8 units of fresh frozen plasma and 2 times 5 units of thrombocyte concentrate, hemostatic control was obtained and the operation could be continued. Paroxetine is a non-tricyclic serotonin reuptake inhibitor prescribed for the treatment of depression. Since this drug also blocks serotonin reuptake in platelets, a clinically significant platelet dysfunction can occur under certain conditions. Because serotonin promotes platelet aggregation, too low an amount of serotonin in the platelets can result in thrombocytopathy. Before major surgery, it is advised to perform extensive clotting tests if there is any hint of haemorrhagic diathesis in the anamnesis. In case of a prolonged bleeding time, paroxetine treatment should be stopped perioperatively.     

Simultaneous thin-layer chromatography-densitometric analysis of sibutramine and citalopram

Due the presence of sibutramine and citalopram in a number of drugs, neurotransmitter reuptake inhibitors. Sibutramine reduces the reuptake of serotonin, norepinephrine, and dopamine; citalopram is an antidepressant drug of the selective serotonin reuptake inhibitor. The thin-layer chromatography-densitometric behavior of some centrally acting serotonin reuptake inhibitors has been studied. The proposed analytical method is suitable for qualitative and quantitative analysis of sibutramine and citalopram.     

Antidepressant Treatment Patterns and Success Rates in a Managed Care Organization

Objective

The purpose of this study was to evaluate the treatment patterns and success rates with antidepressants utilized by patients in a managed care organization (MCO).

Methods

Data were extrapolated from a claims database from an MCO with 225 000 members. Treatment patterns were determined by creating episodes of care for each patient. Successful treatment was defined as a therapeutic dose for at least 180 days of continuous therapy. Success rates were stratified by the type of antidepressant used. Depression-related and total healthcare costs were analyzed in relation to whether a patient’s treatment was successful.

Results

A minority of patients received continuous therapeutic doses for 180 days for their first treatment episode (26.5%) or all treatment episodes of depression (32.9%). Monotherapy was the most common treatment pattern. Treatment with a selective serotonin reuptake inhibitor (SSRI) was associated with a significantly higher success rate than treatment with a tricyclic antidepressant (TCA), in patients with depression (36.6 vs 13.3%). In patients with depression who were receiving SSRIs, the success rates were 37.2% with fluoxetine, 36.2% with paroxetine, and 36.1% with sertraline; there were no significant differences in the success rates among the SSRIs. Patients completing a successful treatment episode were associated with higher pharmacy, depression-related, and total healthcare costs.

Conclusions

Only a minority of patients with depression attained a satisfactory treatment episode with their antidepressant therapy. SSRI therapy was associated with a significantly higher success rate than TCAs. Although monotherapy regimens were the most commonly used treatment strategy, the multivariate analysis reveals that multiple regimen changes (defined as complex in this analysis) may be required to achieve successful treatment. Physicians and MCOs need to monitor patients and be open to necessary regimen changes. Physicians and MCOs must also work together to develop improved strategies to monitor and detect patients with depression who do not comply with their antidepressant regimen.

     

Hallucinations caused by paroxetine taken together with a levodopa-carbidopa preparation

A 79-year-old woman suffering from Parkinson's disease, for which she was taking a levodopa-carbidopa preparation, was prescribed the selective serotonin reuptake inhibitor paroxetine 20 mg once daily. After taking the first tablet she started to suffer from visual hallucinations. Once she stopped taking the paroxetine, the hallucinations ceased immediately. A link between the paroxetine and the hallucinations seemed likely, with a possible interaction between the paroxetine and the levodopa-carbidopa combination.     

Mirtazapine is associated with less anxiolytic use among elderly depressed patients in long-term care facilities

BACKGROUND: Depression is a common, treatable disorder among nursing facility residents. OBJECTIVE: The purpose of this study was to examine medication use and cost between two groups of patients: (1) persons treated with mirtazapine, as compared with (2) persons taking other antidepressants. DESIGN: This study was a retrospective chart review of long-term care patients. Consultant pharmacists collected data on patients who were receiving selective serotonin reuptake inhibitors (SSRIs), venlafaxine, nefazodone, or mirtazapine. SETTING: Nursing facilities that were geographically dispersed throughout the United States. PARTICIPANTS: We studied patients greater than 65 years of age with major depressive disorder or a depression-related diagnosis and receiving antidepressant treatment for at least 3 months. Patients with bipolar-induced depression were excluded as well as those receiving tricyclic antidepressants. RESULTS: The two groups were similar in terms of age, but those receiving mirtazapine had lower body weight and body mass index. Patients on mirtazapine were less likely to be taking a sedative/hypnotic (P = 0.006). This was primarily the result of fewer patients in the mirtazapine group taking lorazepam (P = 0.03). There was no difference between the two groups regarding their use of other psychotropic medications, including multiple antidepressants, antipsychotics, anticonvulsants, acetylcholinesterase inhibitors, or appetite stimulants. Monthly medication costs were less for those patients receiving mirtazapine ($82.83) as compared with other antidepressants ($97.03) (P <0.0001). CONCLUSIONS: The results of this study suggest that patients receiving mirtazapine are less likely to be on anxiolytic/hypnotic agents. The findings also suggest that medication costs are less when mirtazapine is used compared with other antidepressants.     

The business case for quality mental health services: why employers should care about the mental health and well-being of their employees

Employers are very concerned about rising mental health care costs. They want to know whether their health care spending is improving the health of workers, and whether there is a productivity payback from providing good mental health care. This article addresses the subject of employee depression and its impact on business. The literature suggests that depressed individuals exert a significant cost burden for employers. Evidence is mounting that worker depression may have its greatest impact on productivity losses, including increased absenteeism and short-term disability, higher turnover, and suboptimal performance at work. Although there is no conclusive evidence yet that physical health care costs decrease when depression is effectively treated, there is growing evidence that productivity improvements occur as a consequence of effective treatment, and those improvements may offset the cost of the treatment.     

Health Care Utilization and Costs in Patients with Generalized Anxiety Disorder Initiating Add-on Therapy with Benzodiazepines

ObjectivesTo examine patterns of health care utilization and costs in patients with generalized anxiety disorder (GAD) who begin treatment with benzodiazepine anxiolytics as add-on therapy.Study DesignIn a large US health insurance database, we identified all patients with evidence of GAD (International Classification of Diseases, 9^th Revision, Clinical Modification diagnosis code 300.02) who received ≥90 days of therapy with a selective serotonin reuptake inhibitor or venlafaxine between January 1, 2003 and December 31, 2007. Among these patients, we selected those who initiated a course of benzodiazepine add-on therapy. Designating the date of initial receipt of a benzodiazepine as the “index date,” we examined health care utilization and costs over the 6-month period preceding this date (“pre-index”) and the 12-month period following it (“follow-up”).ResultsA total of 2131 patients met all study inclusion criteria. Patients averaged 32 days of therapy with benzodiazepines (median [interquartile range] = 20 [10-30]); 13% of patients received >90 days of therapy, however. In general, levels of health care utilization during the first 6 months of follow-up were higher than those during the pre-index period; between months 7 and 12 of follow-up, however, they were somewhat lower than pre-index levels. Mean (SD) total health care costs were $5148 ($10,658), $6325 ($15,741), and $5373 ($11,230) during pre-index, months 1-6 of follow-up, and months 7-12 of follow-up, respectively.ConclusionsLevels of health care utilization and costs increase following initiation of add-on therapy with a benzodiazepine in patients with GAD receiving selective serotonin reuptake inhibitors or venlafaxine. Although duration of add-on therapy is typically brief, some patients are treated for >90 days, raising potential concerns about risks of dependency and sedation.     

Cost-effectiveness of antidepressant medications

BACKGROUND: Antidepressant medications have been shown to effectively relieve symptoms, improve interpersonal and occupational functioning and reduce disability from coexisting medical conditions. Although the newer selective serotonin reuptake inhibitors (SSRIs) have improved tolerability, are easier to take and are associated with longer lengths of therapy when compared with the tricyclic antidepressants (TCAs), the relative cost-effectiveness of alternative antidepressants remains unclear. AIMS OF THE STUDY: This study seeks to determine (i) the probability that relapse or recurrence of depression can be prevented by appropriate antidepressant choice, (ii) the cost associated with relapse or recurrence of depression and (iii) the relative cost-effectiveness of alternative antidepressants. METHODS: We use a quasi-experimental design to compare claims from a state Medicaid plan for TCA and SSRIs users. RESULTS: Premature discontinuation of antidepressant medication is the strongest predictor of relapse and recurrence. Antidepressant choice was not an independent predictor of relapse or recurrence. The effect of relapse and recurrence on expenditures is complex, with a non-significant trend toward lower expenditures for those who had longer periods between episodes of depression two years after initiation of treatment for the first episode. We were unable to replicate prior research results regarding the impact of SSRIs on duration of therapy in this Medicaid plan. CONCLUSIONS: Premature discontinuation of antidepressant treatment is associated with a high probability of relapse and recurrence. Health care expenditures are not altered by preventing relapse and recurrence. We suggest that antidepressant medications associated with reduced probability of premature discontinuation should be considered cost-effective. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: There are very few variables which health care providers can use to improve the outcomes and associated economic consequences of depression. Among these factors, treatment choice and adherence to the prescribed treatment are likely candidates. In this paper, we suggest that adherence to antidepressant medication results in substantial improvement in the time to relapse or recurrence of depression. Choice of an SSRI may thus improve treatment outcome by lengthening remission. In addition, this choice is not associated with higher costs. IMPLICATIONS FOR HEALTH POLICY FORMULATION: Depressive illnesses are associated with high rates of health service use and functional impairment. Thus, the societal burden is quite high. This paper furthers the debate regarding the relative cost-effectiveness of antidepressant medications, and our findings suggest several ways that policy makers can improve the care of depressed individuals at little additional cost. Specifically our findings highlight the importance of adherence to current recommendations regarding the length of antidepressant treatment and suggest several methods for improving this important outcome. IMPLICATIONS FOR FURTHER RESEARCH: The relative cost-effectiveness of alternative antidepressant medications continues to be an important and unsolved issue. We suggest the need for future research in this area using a variety of research designs appropriate to the question. The quasi-experimental approach outlined here seems promising in this regard.     

Effects of antidepressants on sleep

Insomnia and depression are widespread diseases causing deterioration of life's quality and increasing morbidity and mortality of cardiovascular diseases. Both of them and certain antidepressants adversely affect physiological structure of sleep, while others restore it. The latter drugs must be preferred in therapy of depression accompanying insomnia, and some of them may be effective in treatment of insomnias without depression. Most antidepressants cause REM-reduction, generally with increased serotonin-function. Selective H1-antagonists readily induce sleep, and also the inhibition of cholinergic neurons in the general arousal networks promotes sleep. Sleep continuity is improved by the rise of synaptic level of serotonin. Among tricyclic antidepressants trimipramine and amitriptyline are the best to improve sleep. However, the former has low antidepressant effect and the latter has many adverse side effects. Selective serotonin reuptake inhibitors, except paroxetine, improve sleep only at the time and to the extent of restoring depression. Paroxetine has beneficial effect on sleep at the beginning of the treatment. Mirtazapine is the first-line sleep promoter among atypical antidepressants, however, its effect on increasing appetite markedly limits its application. Trazodone causes hangover, and mianserin may induce restless legs. Insomnias without depression demand lower dose of antidepressants than depression.     

HIV treatment and worker absenteeism: Quasi-experimental evidence from a large-scale health program in South Africa

Over the past decade, large-scale HIV antiretroviral therapy (ART) programs have proven hugely successful in improving the life expectancy of people living with HIV. However, the extent to which treatment allows patients to maintain a productive work life remains an open question. We applied an instrumental variable method based on individual CD4 counts and exogenously changing treatment guidelines to identify the causal effect of ART on health-related absenteeism rates among workers living with HIV. We used monthly data from the occupational health program of one of the world's largest mining companies in South Africa (128,052 observations among 1,924 workers, from 2009 to 2017). Eighteen months after ART initiation, the treatment significantly reduced absenteeism by 1.033 days per worker and month. Using publicly available wage and treatment cost data, we find that the cost savings due to the absenteeism effect of ART alone outweigh treatment costs in the mining sector in several sub-Saharan African countries.     

"We missed you": the absence that fails to make the heart grow fonder

Absenteeism is a problem that costs business in general billions of dollars each year. No industry is immune from its impact, least of all health care. The control of absenteeism rests largely in the hands of the first-line supervisor who must demonstrate visible concern for absenteeism and who must faithfully apply the organization's policies in the correction and control of absenteeism. The keys to absence control are visible concern, reliable documentation, consistent policy application across the work group, and constant attention to employee needs and concerns.     

Efficacy and Acceptability of Pharmacological Treatments for Depressive Disorders in Primary Care: Systematic Review and Network Meta-Analysis

PURPOSEThe purpose of this study was to investigate whether antidepressants are more effective than placebo in the primary care setting, and whether there are differences between substance classes regarding efficacy and acceptability.METHODSWe conducted literature searches in MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and PsycINFO up to December 2013. Randomized trials in depressed adults treated by primary care physicians were included in the review. We performed both conventional pairwise meta-analysis and network meta-analysis combining direct and indirect evidence. Main outcome measures were response and study discontinuation due to adverse effects.RESULTSA total of 66 studies with 15,161 patients met the inclusion criteria. In network meta-analysis, tricyclic and tetracyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), a serotonin-noradrenaline reuptake inhibitor (SNRI; venlafaxine), a low-dose serotonin antagonist and reuptake inhibitor (SARI; trazodone) and hypericum extracts were found to be significantly superior to placebo, with estimated odds ratios between 1.69 and 2.03. There were no statistically significant differences between these drug classes. Reversible inhibitors of monoaminoxidase A (rMAO-As) and hypericum extracts were associated with significantly fewer dropouts because of adverse effects compared with TCAs, SSRIs, the SNRI, a noradrenaline reuptake inhibitor (NRI), and noradrenergic and specific serotonergic antidepressant agents (NaSSAs).CONCLUSIONSCompared with other drugs, TCAs and SSRIs have the most solid evidence base for being effective in the primary care setting, but the effect size compared with placebo is relatively small. Further agents (hypericum, rMAO-As, SNRI, NRI, NaSSAs, SARI) showed some positive results, but limitations of the currently available evidence makes a clear recommendation on their place in clinical practice difficult.     

Depression following a heart infarct and increased risk of death

Depression is an important risk factor for cardiac mortality, especially in the first 18 months after a myocardial infarction. Listlessness and a hostile mood are the specific features of the depression following myocardial infarction, rather than depressed mood. Also, depressed post infarction patients are more often re-admitted for cardiac reasons and their work resumption is delayed. There are indications that depression and myocardial infarction have an aetiological relationship via the behavior and emotions that are a risk factor for the development of both disorders. Depression and myocardial infarction are both stress-related disorders. A pathological stress reaction is seen in both conditions and triggers immune activation, enhanced blood cortisol levels, disturbance of serotonin metabolism and increased sympathetic activation. Early detection of post-infarction depression and treatment with a selective serotonin reuptake inhibitor (SSRI) is advised. SSRIs have been shown to be efficacious and safe in this patient population. Tricyclic antidepressants (TCAs) are relatively contra-indicated due to their cardiac side effects. As yet, no therapeutic effect of antidepressants, in the sense of decreased cardiac mortality or a decrease in fatal rhythm disorders, has been demonstrated.     

Cost-Effectiveness of Repetitive Transcranial Magnetic Stimulation versus Antidepressant Therapy for Treatment-Resistant Depression

BackgroundRepetitive transcranial magnetic stimulation (rTMS) therapy is a clinically safe, noninvasive, nonsystemic treatment for major depressive disorder.ObjectiveWe evaluated the cost-effectiveness of rTMS versus pharmacotherapy for the treatment of patients with major depressive disorder who have failed at least two adequate courses of antidepressant medications.MethodsA 3-year Markov microsimulation model with 2-monthly cycles was used to compare the costs and quality-adjusted life-years (QALYs) of rTMS and a mix of antidepressant medications (including selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, tricyclics, noradrenergic and specific serotonergic antidepressants, and monoamine oxidase inhibitors). The model synthesized data sourced from published literature, national cost reports, and expert opinions. Incremental cost-utility ratios were calculated, and uncertainty of the results was assessed using univariate and multivariate probabilistic sensitivity analyses.ResultsCompared with pharmacotherapy, rTMS is a dominant/cost-effective alternative for patients with treatment-resistant depressive disorder. The model predicted that QALYs gained with rTMS were higher than those gained with antidepressant medications (1.25 vs. 1.18 QALYs) while costs were slightly less (AU $31,003 vs. AU $31,190). In the Australian context, at the willingness-to-pay threshold of AU $50,000 per QALY gain, the probability that rTMS was cost-effective was 73%. Sensitivity analyses confirmed the superiority of rTMS in terms of value for money compared with antidepressant medications.ConclusionsAlthough both pharmacotherapy and rTMS are clinically effective treatments for major depressive disorder, rTMS is shown to outperform antidepressants in terms of cost-effectiveness for patients who have failed at least two adequate courses of antidepressant medications.     

Obsessive-compulsive disorder,trichotillomania, and anorexia nervosa: A case report

We report a case study of an 18-year-old female who presented with symptoms associated with several discrete diagnostic syndromes: obsessive-compulsive disorder, trichotillomania, major depression, and anorexia nervosa. Improvement in each occurred after treatment with the serotonin selective reuptake inhibitor, fluoxetine, suggesting that such syndromes share a common serotonin neurotransmitter disturbance. Furthermore, the combined effects of medication and psychotherapy resulted in improvement in assertiveness, sense of security, self-worth, flexibility, and self-regulation. We discuss the pharmacological and psychotherapeutic implications of possible psychophysiologic similarities among the previously mentioned syndromes. © 1995 by John Wiley & Sons, Inc.     

The practice guideline 'Depressive disorder' (first revision) from the Dutch College of General Practitioners; a response from the perspective of general practice

The revised Dutch College of General Practitioners' practice guideline 'Depressive disorder' no longer distinguishes between mild and severe depression because the management in both cases is identical. This guideline focuses much attention on diagnosis, support and information, all of this in dialogue with the patient. The choice between the antidepressants, a tricyclic antidepressant or a specific serotonin reuptake inhibitor is based on the contraindications of these drugs.