Selective Serotonin Reuptake Inhibitor Drugs Research Articles

Hypothalamic–pituitary–adrenal (HPA) axis function in 3-month old infants with prenatal selective serotonin reuptake inhibitor (SSRI) antidepressant exposure

Background Prenatal exposure to stress and selective serotonin reuptake inhibitors (SSRIs) alter hypothalamic–pituitary–adrenal (HPA) stress reactivity in offspring, however, the effects of combined exposure to HPA activity in human infants is unknown. Objective To examine HPA basal levels and stress responsiveness in 3-month olds with prenatal exposure to SSRIs. Methods Salivary cortisol levels in infants of SSRI treated mothers ( n = 31, mean exposure 230.2 ± 72.2 days) were compared with non-SSRI exposed ( n = 45) infants in response to a challenge (infant-controlled habituation task) and under basal conditions in the late afternoon/early evening. Mode of feeding, to account for possible postnatal drug exposure via breast milk, as well as measures of pre and postnatal maternal mood, were included as covariates. Results Lower post-stress cortisol levels were observed in non-SSRI exposed/non-breastfed infants compared with non-SSRI exposed infants who were breastfed at 3 months of age. Stress reactivity patterns among SSRI exposed infants did not differ with mode of feeding. The cortisol reactivity slope (CRS) was significantly lower among non-SSRI exposed non-breastfed infants compared with non-SSRI exposed breastfed infants. Early evening basal cortisol levels were lower in SSRI exposed infants than in non-SSRI exposed infants, controlling for maternal mood and mode of feeding. Postnatal SSRI exposure (infant SSRI drug levels) via breast milk was not associated with stress or basal cortisol levels. Total cortisol, reflected by the AUC measure, did not differ significantly between exposure groups. Conclusions Prenatal SSRI exposure altered HPA stress response patterns and reduced early evening basal cortisol levels. Stress challenge HPA response differences only became apparent when the moderating effect of method of feeding was accounted for. These findings suggest an early “programming” effect of antenatal maternal mood, prenatal SSRI exposure and postnatal maternal care giving on the HPA system.

Pharmacy and medical costs associated with switching between venlafaxine and SSRI antidepressant therapy for the treatment of major depressive disorder.

While much has been published on utilization of antidepressants and associated resource use, surprisingly little information is available on the relationship between a change in antidepressant agent and health care utilization. Given that many patients will not respond to initial therapy (and therefore would be candidates for switching treatment) and the array of antidepressant medications on the market, information on the impact of switching would be beneficial to both providers and policymakers. To explore patterns of antidepressant drug use and depression-related and all-cause medical costs for patients who switched therapy between 2 drug classes, selective serotonin reuptake inhibitors (SSRIs) and the selective norepinephrine reuptake inhibitor (SNRI) venlafaxine. Using an administrative claims database of 36 million members from 61 health plans, this retrospective cohort analysis examined patients who had (1) a diagnosis of major depressive disorder (MDD, International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 296.2x for MDD single episode, 296.3x for MDD recurrent episode, 300.4 for dysthymic disorder, and 311 for depressive disorder not elsewhere classified) and (2) a newly prescribed antidepressant during the year 2002. Costs were defined as amounts paid by health plans for all inpatient, outpatient, physician and pharmacy services (i.e., allowed charges after subtraction of member cost-share). Depression-related costs were defined using (1) medical claims with primary diagnosis of depression and (2) pharmacy claims for antidepressants. Using an index date of the first antidepressant claim, 12 months of pre-index and postindex data were available for all eligible patients. Switching was defined as occurring between the SSRIs and venlafaxine (i.e., patients who switched within the SSRI drug class across different SSRIs were treated as non-switchers until they switched to venlafaxine), and there was no minimum or maximum gap in therapy. The SSRIs included fluoxetine, citalopram, sertraline, and paroxetine; the only SNRI on the market at the time was venlafaxine. Multivariate regression analyses determined predictors of switching and factors influencing overall and depression-related costs, while controlling for confounding factors. For the 12-month period following the index date (fixed length of follow-up), the study compared per-patient per-year (PPPY) costs for (1) patients who switched versus those who did not switch and (2) patients with single versus multiple trials of SSRI for the subgroup of patients who switched from an SSRI to venlafaxine. For the time periods before versus after the switch (variable lengths of follow-up), per-patient means and medians of monthly cost averages (with follow-up periods <1 month set to 1 month for 16.5% [n=272] of SSRI-to-venlafaxine switchers and 14.1% [n=103] of venlafaxine-to-SSRI switchers) were calculated for the subgroup of patients who made a switch. A total of 48,950 patients were included in the study, with 43,653 (89.2%) treated first with SSRIs and 5,297 (10.8%) treated first with venlafaxine. Of the initial SSRI users, 1,645 (3.8%) switched to venlafaxine, and of the initial venlafaxine users, 733 (13.8%) switched to an SSRI. Mean (standard deviation [SD]) 12-month total (medical plus pharmacy) depression-related costs in 2002-2003 dollars were 118.0% higher for SSRI switchers ($1,225 [$3,438] vs. $562 [$2,153], P<0.001) and 18.4% higher for venlafaxine switchers ($863 [$1,503] vs. $729 [$1,185], P=0.021) as compared with non-switchers. From the pre-switch to post-switch periods, depression-related mean monthly medical costs declined by 66.4% among switchers from SSRIs ($113 [$912] vs. $38 [$347], P=0.001) and by 61.1% among switchers from venlafaxine ($54 [$299] vs. $21 [$138], P=0.005). Monthly mean depression-related pharmacy costs increased by 62.2% following a switch from an SSRI to venlafaxine (from $45 [$38] to $73 [$62], P<0.001) and declined by 17.3% following a switch from venlafaxine to an SSRI (from $52 [$45] to $43 [$38], P<0.001). After adjustment for multiple covariates including demographic characteristics, 10 selected comorbidities, and physician specialty, general linear models with log-transformed costs as the dependent variables demonstrated significant associations between switching and total costs (both all-cause and depression-related) in both the SSRI and the venlafaxine cohorts. Although relatively few patients switched antidepressant drug classes, patients who made a switch had higher all-cause health care costs and higher depression-related costs than patients who did not switch. Switching drug classes was associated with lower mean monthly depression-related health care costs following the switch. For those patients switching from an SSRI to venlafaxine, mean medical cost reductions offset higher pharmacy costs; for patients switching from venlafaxine to an SSRI, mean medical and pharmacy costs declined.

Selective serotonin re-uptake inhibitors (SSRIs) versus placebo for obsessive compulsive disorder (OCD)

Obsessive compulsive disorder is a common and disabling disorder. A significant proportion of patients manifest a chronic course. Individual randomised controlled trials (RCTs) have shown that selective serotonin re-uptake inhibitors (SSRIs) are effective in this condition. Previous systematic reviews or meta-analyses summarising the evidence are methodologically problematic or limited in the scope of their analysis. To examine the efficacy and adverse effects of serotonin re-uptake inhibitors (SSRIs) versus placebo for obsessive compulsive disorder (OCD) in adults. CCDANCTR-Studies and CCDANCTR-References were searched on 12/11/2007. Reference lists were checked. Experts in the field were contacted. All RCTs and quasi-RCTs examining the efficacy of SSRIs compared with placebo for OCD in adults were eligible for inclusion. Selection of studies and data extraction were carried out by two review authors independently, and quality assessment of studies was undertaken. Data analysis was conducted using Review Manager software. Summary measures were produced using the weighted mean difference (WMD) for continuous data and relative risk (RR) for dichotomous data, with 95% confidence intervals (CI). SSRIs were examined as an overall group of drugs, and as individual drugs. Seventeen studies were included in the review, involving 3097 participants. Based on all 17 studies, SSRIs as a group were more effective than placebo in reducing the symptoms of OCD between 6 and 13 weeks post-treatment, measured using the Yale-Brown Obsessive Compulsive Scale (YBOCS) (WMD -3.21, 95% CI -3.84 to -2.57). The WMD for individual SSRI drugs were similar and not statistically different. Based on 13 studies (2697 participants), SSRIs were more effective than placebo in achieving clinical response at post-treatment (RR 1.84, 95% CI 1.56 to 2.17). The pooled RR was shown to be similar between individual SSRI drugs. Although reported adverse effects data were more limited, with few exceptions, the overall and individual adverse effects for the different SSRIs were always worse than for placebo and, in the majority of cases, the difference was statistically significant. Nausea, headache and insomnia were always reported amongst the most common adverse effects in trials of each of the drugs. SSRIs are more effective than placebo for OCD, at least in the short-term, although there are differences between the adverse effects of individual SSRI drugs. The longer term efficacy and tolerability of different SSRI drugs for OCD has yet to be established.

Recommendations from the EGAPP Working Group: testing for cytochrome P450 polymorphisms in adults with nonpsychotic depression treated with selective serotonin reuptake inhibitors

This statement summarizes the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group recommendations regarding CYP450 genetic testing in adult patients beginning treatment with selective serotonin reuptake inhibitors (SSRIs), and the supporting scientific evidence. EGAPP is a project developed by the National Office of Public Health Genomics at the Centers for Disease Control and Prevention to support a rigorous, evidence-based process for evaluating genetic tests and other genomic applications that are in transition from research to clinical and public health practice in the United States. A key goal of the EGAPP Working Group is to develop conclusions and recommendations regarding clinical genomic applications and to establish clear linkage to the supporting scientific evidence. The Working Group members are nonfederal experts in genetics, laboratory medicine, and clinical epidemiology convened to establish methods and processes; set priorities for review topics; participate in technical expert panels for commissioned evidence reviews; publish recommendations; and provide guidance and feedback on other project activities.Summary of Recommendation The EGAPP Working Group found insufficient evidence to support a recommendation for or against use of CYP450 testing in adults beginning SSRI treatment for non-psychotic depression. In the absence of supporting evidence, and with consideration of other contextual issues, EGAPP discourages use of CYP450 testing for patients beginning SSRI treatment until further clinical trials are completed. RationaleThe EGAPP Working Group found no evidence linking testing for CYP450 to clinical outcomes in adults treated with SSRIs. While some studies of a single SSRI dose in healthy patients report an association between genotypic CYP450 drug metabolizer status and circulating SSRI levels, this association was not supported by studies of patients receiving ongoing SSRI treatment. Further, CYP450 genotypes are not consistently associated with the patient outcomes of interest, including clinical response to SSRI treatment or adverse events as a result of treatment. No evidence was available showing that the results of CYP450 testing influenced SSRI choice or dose and improved patient outcomes, or was useful in medical, personal, or public health decision-making. In the absence of evidence supporting clinical utility, it is not known if potential benefits from CYP450 testing will outweigh potential harms. Potential harms may include increased cost without impact on clinical decision making or improvement in patient outcomes, less effective treatment with SSRI drugs, or inappropriate use of genotype information in the management of other drugs metabolized by CYP450 enzymes.

Delivery Outcome in Relation to Maternal Use of Some Recently Introduced Antidepressants

Little is known concerning possible hazards of maternal use of the recently introduced antidepressant drugs with noradrenergic and varying serotonergic activity (serotonin-noradrenaline reuptake inhibitor [SNRI]/noradrenergic reuptake inhibitor [NRI] drugs). Using the Swedish Medical Birth Registry, we identified 732 women who had used SNRI/NRI drugs in early pregnancy. Maternal characteristics were studied as well as delivery outcome: pregnancy duration, birth weight, neonatal diagnoses, infant deaths, and congenital malformations. Comparisons were made with all deliveries in the population (n = 860,215) after adjustment for identified confounders, and risks were expressed as odds ratios or (when numbers were low) as risk ratios. Women using SNRI/NRI deviated from other women by being older, more often having their first infant, being more extensive smokers, having a higher body mass index, and more often being born within Sweden. These characteristics, like the pattern of concomitant drug use, resembled much those of women using selective serotonin reuptake inhibitor (SSRI) drugs. The rate of preterm births was significantly increased (odds ratio, 1.6; 95% confidence interval, 1.19-2.15), and neonatal symptoms such as respiratory problems, low Apgar score, hypoglycemia, and neonatal convulsions showed a similar pattern as seen after maternal SSRI treatment. We found no increased risk for stillbirths or congenital malformations. Delivery outcome after exposure to SNRI/NRI drugs resembles much what has been described after use of SSRI drugs. No signs of teratogenicity were found.

Efficacy of cognitive-behavioral and pharmacological treatments for children with social anxiety

Childhood social anxiety is associated with significant social and academic impairment. The purpose of this study was to compare and contrast the efficacy of two major treatments for social anxiety disorders in children: cognitive-behavioral therapy and selective serotonin reuptake inhibitor (SSRI) drug treatment. Treatment studies in the literature were evaluated using meta-analytic techniques to compare pre- and post-treatment measures of social anxiety symptoms, general anxiousness, social competency, and impairment. Results indicate that the core symptoms of social anxiety and impairment were reduced by both cognitive-behavioral treatment (ES=0.86 and 1.56) and SSRI treatment (ES=1.30 and 2.29), respectively. Similarly, peripheral symptoms of general anxiousness were reduced by both cognitive-behavioral treatment (ES=0.75) and SSRI treatment (ES=1.29). Finally, both cognitive-behavioral (ES=0.68) and SSRI treatment (ES=0.68) resulted in moderate improvements in social competence. Implications and the limitations of these meta-analytic findings are discussed with respect to the evidence-based intervention movement.

Safety and Efficacy of Escitalopram in the Treatment of Premature Ejaculation

Purpose:To evaluate the efficacy and safety of most selective serotonin reuptake inhibitor drug, escitalopram, in delaying ejaculation in patients with premature ejaculation (PE).Materials and Methods:A total of 276 married men (mean age, 34.4 years) with PE were randomly assigned to receive 10 mg o

The safety of antidepressant drugs during pregnancy

This article discusses known or suspected effects of maternal use of antidepressants during pregnancy on pregnancy outcome. It is unlikely that any marked teratogenic effect occurs with the possible exception of an increased risk for cardiovascular defects after maternal use of clomipramine or paroxetine. An increased risk for preterm birth is seen. Transient neonatal symptoms are common after the use of antidepressants in late pregnancy. Few firm data are available on the possible impact on the long-term neuropsychological development of the infants. The magnitude of the actual contribution from drug therapy is unclear; it is likely that the underlying pathology of the mother explains part of the anomalies. Selective serotonin re-uptake inhibitor drugs seem to represent a smaller hazard than tricyclic antidepressants. Further research to separate the effects of the drug and underlying pathology is urgently needed as are large-scale studies on long-term development. When a pregnant woman has a major depressive disease and non-pharmacological treatments are not enough, the relatively small risk with drug therapy has to be weighed against the considerable risk for a relapse of the disease if therapy is interrupted.

Selective Serotonin Reuptake Inhibitors and Risk of Acute Pancreatitis

To examine whether use of selective serotonin reuptake inhibitors (SSRIs) is associated with acute pancreatitis, a population-based case-control study was conducted in the counties of North Jutland (data 1991-2003), Aarhus (data 1996-2003), and Viborg (data 1998-2003), Denmark. Through hospital discharge registries, we identified all patients with an incident hospitalization of acute pancreatitis. From the Civil Registration System, we selected 10 sex- and age-matched population controls per case using risk set sampling. All prescriptions of SSRI and other antidepressant drugs within 90 days (present users) or 91 to 365 days (former users) before admission with acute pancreatitis, or index date among controls, were collected from prescription databases. First-time users were defined as those who redeemed their first SSRI prescription within 14 days before admission/index date. We estimated the relative risk of acute pancreatitis after exposure to SSRI or other antidepressants, adjusting for potential confounders. We included 3083 cases of acute pancreatitis and 30,830 controls. The adjusted odds ratio (OR) for acute pancreatitis in present users of SSRI was 1.2 (95% confidence interval [CI], 1.0-1.5); for former users, the adjusted OR was 1.2 (95% CI, 0.9-1.7). For current and former users of other antidepressant drugs, the corresponding adjusted ORs were 1.4 (95% CI, 1.1-1.7) and 1.4 (95% CI, 1.0-1.9), respectively. The adjusted OR of acute pancreatitis in first-time users of SSRI was 2.8 (95% CI, 1.1-7.0). We found use of SSRIs to be associated with increased risk for acute pancreatitis. However, the estimate did not differ between present or former users of SSRI and was not materially different from the estimate in users of other antidepressant drugs. Therefore, our data suggest that the increased risk is related to confounding by lifestyle factors or the underlying depression.

Amperometric responses of CYP2D6 drug metabolism nanobiosensor for sertraline: a selective serotonin reuptake inhibitor

Sertraline is selective serotonin reuptake inhibitor drug marketed as Zoloft by Pfizer and used mainly for the treatment of depression, anxiety and obsession. A number of side effects are associated with the use of the drug including gastrointestinal complaints, nervousness and sexual dysfunction. This means that a reliable fast method (such as biosensing) for determining sertraline metabolic profile of patients is essential for adequate dosing. Nanobiosensor for the determination of sertraline biotransformation was prepared with cytochrome P450-2D6 (CYP2D6) and poly(8-anilino-1-napthalene sulphonic acid) nanotubes (90 nm in diameter and 600-800 nm in length) potentiodynamically deposited on gold. The biosensor gave a linear response over the concentration range of 0.2 and 1.4 microM with a sensitivity value of 0.301 microA/microM and a detection limit of 0.13 microM. The nanobiosensor exhibited substrate inhibition response profile for sertraline biotransformation at high concentrations. Analysis of the Michaelis-Menten region of the nanosensor response curve for sertraline gave an apparent Michaelis-Menten constant (K(m)) value of 0.75 microM, which is higher than the peak plasma concentration (C(max)) value of 0.55 microM, thereby making the sensor suitable for sertraline determination in serum.

Genetic screening for SSRI drug response among those with major depression: great promise and unseen perils

This article examines evidence for the potential benefit of genetic testing for SSRI response, as well as potential ethical and practical implications of the implementation of this test into standard psychiatric practice. We reviewed three areas of the literature: the burden of treatment-resistant and treatment-intolerant major depressive disorders, the evidence for the value of genetic testing to predict drug response, and the ethical and practical issues of genetic testing in usual care. Treatment resistance and treatment intolerance are common for persons treated with selective serotonin reuptake inhibitors (SSRIs) and are associated with both financial and quality-of-life costs. There is strong evidence from association studies that some polymorphisms are associated with SSRI response. However, no randomized trials have yet tested the efficacy of genetic tests to improve outcome in those with treatment resistance or treatment intolerance to SSRIs. Given the nonspecific nature of the test proposed, several ethical concerns are also involved with administering the genetic tests to patients. A randomized trial comparing response in those treated with standard psychiatric care and in those treated with psychiatric care tailored as a result of genetic test results should be completed before the implementation of these tests can be considered. Additionally, the ethical and practical questions concerning the tests must be addressed now, so that the potential impact of these tests on patient care can be well understood prior to adoption in standard practice.

Obesity, Dyslipidemia, and Diabetes With Selective Serotonin Reuptake Inhibitors

This study aimed to examine whether subjects taking selective serotonin reuptake inhibitors (SSRIs) are more likely to have elements of the metabolic syndrome compared with those taking no psychotropic drugs. For comparison, we also studied subjects taking antipsychotic drugs. We used data from The Hordaland Health Study '97-'99, a general community cross-sectional health survey including 25,315 subjects aged 40 to 49 and 70 to 74 years. For the groups studied, we estimated prevalence and odds ratios (ORs) for obesity, hypercholesterolemia, low high-density lipoprotein cholesterol, hyper-triglyceridemia, and diabetes. We observed an association between use of SSRIs as a group (N = 461) and abdominal obesity (OR = 1.40, 95% CI = 1.08 to 1.81) and hypercholesterolemia (OR = 1.36, 95% CI = 1.07 to 1.73) after adjusting for multiple possible confounders. There was also a trend toward an association between SSRI use and diabetes. In a subgroup analysis of subjects taking SSRIs, the use of paroxetine (N = 187) was markedly associated with both general and abdominal obesity but not with hypercholesterolemia. In contrast, the use of citalopram (N = 142) was not associated with any of the metabolic outcome variables, while the use of any other SSRI (sertraline, fluoxetine, or fluvoxamine) (N = 131) as a mixed subgroup was associated with both abdominal obesity and hypercholesterolemia. We also replicated the previously reported associations between use of antipsychotics and obesity and metabolic disturbances. We have shown that use of at least some SSRIs is associated with clinical and biochemical elements of the metabolic syndrome. Our data indicate differences in the metabolic side effect profile among various SSRI drugs, although treatment bias might have influenced these results. We suggest that patients taking SSRIs be carefully monitored for obesity and dyslipidemia.

WITHDRAWN: Selective serotonin reuptake inhibitors (SSRIs) versus other antidepressants for depression.

The relatively new class of antidepressant, the selective serotonin reputake inhibitors (SSRIs), may be better tolerated than the older tricyclic antidepressants. This review compares the efficacy of SSRIs with other antidepressants. To examine the relative efficacy of selective serotonin reuptake inhibitors (SSRIs) compared to other antidepressants. The search strategy included a search of (a) Electronic bibliographic databases (MEDLINE, EMBASE); (b) reference lists of related reviews (c) reference lists of all located studies (d) contact with the manufacturer and (e) the Cochrane Group register of controlled trials Randomised controlled trials comparing selective serotonin reuptake inhibitors with other kinds of antidepressants in the treatment of patients with depressive disorders. The outcome measures assessed included measures of the severity of depression. Data were collected from each study the main outcome measurefrom each study. These included: mean Hamilton depression rating scale, mean Montgomery & Asberg depression rating scale, Clinical Global Impression rating scale. An analysis of standardised mean difference of these scales was performed using Review Manager 3.1 software. The presence of heterogeneity of treatment effect was assessed Ninety-eight trials contributed data to the analysis of the relative efficacy of SSRIs and related drugs with comparator antidepressants (Figure 3 & Appendix 3). Analysis of efficacy was based upon 5044 patients treated with an SSRI or related drug, and 4510 treated with an alternative antidepressant. The standardised effect size for SSRIs and related drugs together versus alternative antidepressants using a fixed effects model was 0.035 (95% CI -0.006 to 0.076; Q = 149.25, df = 97, p < 0.001). There are no clinically significant differences in effectiveness between selective serotonin reuptake inhibitors and tricyclic antidepressants. Treatment decisions need to be based on considerations of relative patient acceptability, toxicity and cost.

Efficacy of type‐5 phosphodiesterase inhibitors in the drug treatment of premature ejaculation: a systematic review

This review examines the role of nitric oxide (NO) as a neurotransmitter involved in the central and peripheral control of ejaculation, the methods of phosphodiesterase type 5 inhibitor (PDE5I) drug treatment studies for premature ejaculation (PE), the adherence of methods to the contemporary consensus of ideal PE drug trial design, the impact of methods on treatment outcomes and the role of PDE5Is in the treatment of PE. NO/cGMP transduction is involved in both the central and peripheral control of emission, but evidence for a direct central or peripheral effect of PDE5Is on ejaculation is speculative. Thirteen of the 14 studies reviewed failed to fulfil the evidence-based medicine criteria for ideal PE drug trial design. Limitations of the studies include inadequately defined study populations, the lack of a double-blind placebo-controlled study design, and the absence of consistent objective physiological measures or sensitive, validated outcome assessment instruments as study endpoints. The broad range of intravaginal ejaculatory latency time (IELT) fold-increases reported with PDE5Is, on-demand selective serotonin re-uptake inhibitor (SSRI) drugs, and combined PDE5I/on-demand SSRIs is testament to the unreliability of data and conclusions from methodologically flawed studies. The one study that fulfilled the evidence-based medicine criteria of an ideal clinical trial design reported that treatment with sildenafil failed to significantly increase baseline IELT, supporting our conclusion that there is no convincing evidence to support any role for PDE5Is in the treatment of men with lifelong PE and normal erectile function. However, there is limited evidence to support a potential role for PDE5Is alone or combined with daily or on-demand SSRIs in the treatment of acquired PE in men with comorbid erectile dysfunction. Further controlled studies adhering to the contemporary consensus of ideal clinical trial design are required to clarify the role of PDE5Is in this subgroup of men with acquired PE.

Initial results of the use of prescription order change forms to achieve dose form optimization (consolidation and tablet splitting) of SSRI antidepressants in a state Medicaid program.

One method to reduce drug costs is to promote dose form optimization strategies that take advantage of the flat pricing of some drugs, i.e., the same or nearly the same price for a 100 mg tablet and a 50 mg tablet of the same drug. Dose form optimization includes tablet splitting; taking half of a higher-strength tablet; and dose form consolidation, using 1 higher-strength tablet instead of 2 lower-strength tablets. Dose form optimization can reduce the direct cost of therapy by up to 50% while continuing the same daily dose of the same drug molecule. To determine if voluntary prescription change forms for antidepressant drugs could induce dosing changes and reduce the cost of antidepressant therapy in a Medicaid population. Specific regimens of 4 selective serotonin reuptake inhibitors (SSRIs)- citalopram, escitalopram, paroxetine, and sertraline- were identified for conversion to half tablets or dose optimization. Change forms, which served as valid prescriptions, were faxed to Oregon prescribers in October 2004. The results from both the returned forms and subsequent drug claims data were evaluated using a segmented linear regression. Citalopram claims were excluded from the cost analysis because the drug became available in generic form in October 2004. A total of 1,582 change forms were sent to 556 unique prescribers; 9.2% of the change forms were for dose consolidation and 90.8% were for tablet splitting. Of the 1,118 change forms (70.7%) that were returned, 956 (60.4% of those sent and 85.5% of those returned) authorized a prescription change to a lower-cost dose regimen. The average drug cost per day declined by 14.2%, from Dollars 2.26 to Dollars 1.94 in the intervention group, versus a 1.6% increase, from Dollars 2.52 to Dollars 2.56, in the group without dose consolidation or tablet splitting of the 3 SSRIs (sertraline, escitalopram, and immediate-release paroxetine). Total drug cost for the 3 SSRIs declined by 35.6%, from Dollars 333,567 to Dollars 214,794, as a result of a 24.8% decline in the total days of SSRI drug therapy and the 14.2% decline in average SSRI drug cost per day. The estimated monthly cost avoidance from this intervention, based on pharmacy claims data, was approximately Dollars 35,285, about 2% of the entire spending on SSRI drugs each month, or about Dollars 0.09 per member per month. Program administration costs, excluding costs incurred by prescribers and pharmacy providers, were about 2% of SSRI drug cost savings. Voluntary prescription change forms appear to be an effective and well-accepted tool for obtaining dose form optimization through dose form consolidation and tablet splitting, resulting in reduction in the direct costs of SSRI antidepressant drug therapy with minimal additional program administration costs.

The Effect of Early Poststressor Intervention with Sertraline on Behavioral Responses in an Animal Model of Post-Traumatic Stress Disorder

Whereas several well-controlled studies have established the selective serotonin reuptake inhibitors (SSRIs) as the recommended first-line pharmacotherapeutic agents for acute and chronic post-traumatic stress disorder (PTSD), drug interventions in the acute postexposure phase have not been studied to the same extent and tend to be largely speculative. This study employed an animal model which assesses prevalence of individual stress-response behavior patterns in order to assess the short-term effects of a brief treatment regimen with an SSRI (sertraline) administered immediately after stress-exposure, with those of an identical delayed regimen and of saline. Prevalence rates of rats displaying extreme anxiety-like behavioral responses to predator stress, compared to partial and minimal responses, were assessed in the elevated plus maze and startle response paradigms, with and without intraperitoneal administration of sertraline for 7 days immediately postexposure, or 7 days after exposure. Immediate postexposure administration of sertraline reduced anxiety-like and avoidant behavior, decreased hyperarousal responses and diminished the overall incidence of extreme (PTSD-like) behavioral responses, compared to the delayed treatment regimen and to saline controls. Brief immediate poststress exposure treatment with sertraline reduced prevalence rates of extreme behavioral disruption in the short-term. SSRI drugs are thus worthy of further investigation as agents of secondary prevention in the acute aftermath of stress-exposure.

Manufacturing Consensus

The Food and Drug Administration (FDA) has declared that it would be illegal to advertise as or in any way claim your drug to be superior to competitors on the market, which are up to 30 times cheaper. How does a pharmaceutical company market such a product? The answer is to enlist academics to form expert panels to construct guidelines and algorithms, or participate in Delphi panels and other exercises, which can be expected to prove that newer, more costly drugs produce cost savings. These academics do so on the basis of the existing clinical trial evidence--which supposedly the FDA has used to come to its verdict that the newer compound is no better than its competitors. However, where the FDA has seen the raw data, academics later see the published data. In between intervenes a medical writing exercise, which produces the first and most important piece of advertising for any pharmaceutical product--the randomized controlled trial infomercial. This paper explores how pharmaceutical companies manufacture an apparent academic consensus and, in so doing, gives a case study of the recent controversies surrounding the marketing of selective serotonin reuptake inhibitor (SSRI) drugs for adolescent depression.

Spectrophotometric Analysis of Selective Serotonin Reuptake Inhibitors Based on Formation of Charge-Transfer Complexes with Tetracyanoquinodimethane and Chloranilic Acid

A simple, accurate, and sensitive spectrophotometric method for analysis of selective serotonin reuptake inhibitors (SSRIs) has been developed and validated. The analysis was based on the formation of colored charge-transfer complexes between the intact molecule of SSRI drug as an n-electron donor and each of tetracyanoquinodimethane (TCNQ) or p-chloranilic acid (pCA) as electron acceptors. The formed complexes were measured spectrophotometrically at 842 and 520 nm for TCNQ and pCA, respectively. Different variables and parameters affecting the reactions were studied and optimized. Under the optimum reaction conditions, linear relationships with good correlation coefficients (0.9975-0.9996) were found between the absorbances and the concentrations of the investigated drugs in the concentration ranges of 4-50 and 20-400 microg/mL with TCNQ and pCA, respectively. With all the investigated drugs, TCNQ gave more sensitive assays than pCA; the limits of assay detection were 2.5-4.8 and 20-40 microg/mL with TCNQ and pCA, respectively. The intra- and interassay precisions were satisfactory; the relative standard deviations did not exceed 2%. The proposed procedures were successfully applied to the analysis of the studied drugs in pure form and pharmaceutical formulations with good accuracy; the recovery values were 98.4-102.8 +/- 1.24-1.81%. The results obtained from the proposed method were statistically comparable with those obtained from the previously reported methods.

Chlorpheniramine, selective serotonin-reuptake inhibitors (SSRIs) and over-the-counter (OTC) treatment

Some old antihistamines were selective serotonin-reuptake inhibitors (SSRIs) and the SSRI effect was discovered by Nobel Laureate Professor Arvid Carlsson as early as 1969. Chlorpheniramine was the most active of the tested drugs, and it compares favourably with amitriptyline and imipramine with respect to actions on both serotonergic and noradrenergic neurons. Chlorpheniramine can be called a SSRI, since the blocking of 5HT is stronger than the effect on noradrenaline neurons; however it might also be called a selective serotonin and noradrenaline reuptake inhibitor (SSNRI) and be compared with new drugs, such as venlafaxine. Carlsson suggested the potential value of clinical studies of the antidepressant properties of this and related antihistamine drugs. But, in the event, no such trials were ever performed at the time. However, later clinical observations of the benefits of dex-chlorpheniramine treatment in panic disorder have been published. Clinical experience suggests that patients using chlorpheniramine, and having also a concomitant depression or panic disorder, may experience a return of symptoms when their old drug is changed to a new antihistamine lacking SSRI effects. Yet this phenomenon is not known to many doctors, and even less known to the large number of patients buying chlorpheniramine under various trade names over-the-counter (OTC) at a low price for self-treatment of hay fewer or as a cold remedy. Chlorpheniramine was introduced in USA under the name Chlor-Trimeton as long ago as July 1950, and is still on the market. Therefore, this SSRI is now over 50 years old. If chlorpheniramine had been tested in depression in the nineteen seventies, it is probable that a safe, inexpensive SSRI drug could have been used some 15 years earlier than fluoxetine - which became available in 1987. Chlorpheniramine might have been the first safe, non-cardiotoxic and well-tolerated antidepressant. Billions of dollars in the development and marketing costs would have been saved, and the suffering of millions of patients alleviated.

Effect of gender on antinociceptive effect of paroxetine in hot plate test in mice

Purpose Many studies have reported both a gender difference in the rates of depression and its treatment by using any of the widely used antidepressant drug groups. Some studies suggest that females respond more poorly to tricyclic antidepressants than males and appear to respond better to selective serotonin reuptake inhibitors (SSRI). There is no study investigating the analgesic/antinociceptive effects of antidepressant drugs on the basis of gender difference. In this study, we aimed to investigate the antinociceptive effect of paroxetine on the basis of gender difference. Methods The antinociceptive effect of paroxetine was tested using hot plate test in Balb/c mice (30–40 g). The animals were divided into eight groups on the basis of gender. Findings While paroxetine did not induce an antinociceptive effect in both sex at a dose of 1 mg kg − 1 , it showed significant antinociceptive effects in both sex at a dose of 5 or 10 mg kg − 1 . None of the doses of paroxetine revealed a gender difference in its antinociceptive action. Conclusion There are several studies showing positive or negative evidence on the gender difference of paroxetine's antidepressant effect, but in the literature there is no study about the gender difference of paroxetine's or any other SSRI drug's antinociceptive effect. In conclusion, our results do not show any gender difference in antinociceptive effect of paroxetine that may be important especially when it would be used as an adjuvant agent in some painful conditions.