Selective Serotonin Reuptake Inhibitors Agents Research Articles

Pharmacotherapy for post traumatic stress disorder (PTSD).

Posttraumatic stress disorder (PTSD) is a prevalent and disabling disorder. Evidence that PTSD is characterised by specific psychobiological dysfunctions has contributed to a growing interest in the use of medication in its treatment. To assess the effects of medication for reducing PTSD symptoms in adults with PTSD. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 11, November 2020); MEDLINE (1946-), Embase (1974-), PsycINFO (1967-) and PTSDPubs (all available years) either directly or via the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR). We also searched international trial registers. The date of the latest search was 13 November 2020. All randomised controlled trials (RCTs) of pharmacotherapy for adults with PTSD. Three review authors (TW, JI, and NP) independently assessed RCTs for inclusion in the review, collated trial data, and assessed trial quality. We contacted investigators to obtain missing data. We stratified summary statistics by medication class, and by medication agent for all medications. We calculated dichotomous and continuous measures using a random-effects model, and assessed heterogeneity. We include 66 RCTs in the review (range: 13 days to 28 weeks; 7442 participants; age range 18 to 85 years) and 54 in the meta-analysis. For the primary outcome of treatment response, we found evidence of beneficial effect for selective serotonin reuptake inhibitors (SSRIs) compared with placebo (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.59 to 0.74; 8 studies, 1078 participants), which improved PTSD symptoms in 58% of SSRI participants compared with 35% of placebo participants, based on moderate-certainty evidence. For this outcome we also found evidence of beneficial effect for the noradrenergic and specific serotonergic antidepressant (NaSSA) mirtazapine: (RR 0.45, 95% CI 0.22 to 0.94; 1 study, 26 participants) in 65% of people on mirtazapine compared with 22% of placebo participants, and for the tricyclic antidepressant (TCA) amitriptyline (RR 0.60, 95% CI 0.38 to 0.96; 1 study, 40 participants) in 50% of amitriptyline participants compared with 17% of placebo participants, which improved PTSD symptoms. These outcomes are based on low-certainty evidence. There was however no evidence of beneficial effect for the number of participants who improved with the antipsychotics (RR 0.51, 95% CI 0.16 to 1.67; 2 studies, 43 participants) compared to placebo, based on very low-certainty evidence. For the outcome of treatment withdrawal, we found evidence of a harm for the individual SSRI agents compared with placebo (RR 1.41, 95% CI 1.07 to 1.87; 14 studies, 2399 participants). Withdrawals were also higher for the separate SSRI paroxetine group compared to the placebo group (RR 1.55, 95% CI 1.05 to 2.29; 5 studies, 1101 participants). Nonetheless, the absolute proportion of individuals dropping out from treatment due to adverse events in the SSRI groups was low (9%), based on moderate-certainty evidence. For the rest of the medications compared to placebo, we did not find evidence of harm for individuals dropping out from treatment due to adverse events. The findings of this review support the conclusion that SSRIs improve PTSD symptoms; they are first-line agents for the pharmacotherapy of PTSD, based on moderate-certainty evidence. The NaSSA mirtazapine and the TCA amitriptyline may also improve PTSD symptoms, but this is based on low-certainty evidence. In addition, we found no evidence of benefit for the number of participants who improved following treatment with the antipsychotic group compared to placebo, based on very low-certainty evidence. There remain important gaps in the evidence base, and a continued need for more effective agents in the management of PTSD.

Secondary and side effects of particular Selective Serotonin Reuptake Inhibitors (SSRIs) antidepressants - literature review

Serotonin reuptake inhibitors (SSRIs), along with serotonin norepinephrine reuptake inhibitors (SNRIs) and norepinephrine dopamine reuptake inhibitors (NDRIs), are the first-line drugs in the treatment of depression. Pharmacotherapy of psychiatric disorders with SSRIs is widely practised. Although SSRIs are thought to be relatively safe group of drugs, it is worth to remember that particular SSRIs agents are related to unique secondary and side effects. Knowledge about basic differences between each medication in this group is essential to choose suitable treatment for every patient.

Pretreatment Reward Sensitivity and Frontostriatal Resting-State Functional Connectivity Are Associated With Response to Bupropion After Sertraline Nonresponse

BackgroundStandard guidelines recommend selective serotonin reuptake inhibitors as first-line antidepressants for adults with major depressive disorder, but success is limited and patients who fail to benefit are often switched to non–selective serotonin reuptake inhibitor agents. This study investigated whether brain- and behavior-based markers of reward processing might be associated with response to bupropion after sertraline nonresponse. MethodsIn a two-stage, double-blinded clinical trial, 296 participants were randomized to receive 8 weeks of sertraline or placebo in stage 1. Individuals who responded continued on another 8-week course of the same intervention in stage 2, while sertraline and placebo nonresponders crossed over to bupropion and sertraline, respectively. Data from 241 participants were analyzed. The stage 2 sample comprised 87 patients with major depressive disorder who switched medication and 38 healthy control subjects. A total of 116 participants with major depressive disorder treated with sertraline in stage 1 served as an independent replication sample. The probabilistic reward task and resting-state functional magnetic resonance imaging were administered at baseline. ResultsGreater pretreatment reward sensitivity and higher resting-state functional connectivity between bilateral nucleus accumbens and rostral anterior cingulate cortex were associated with positive response to bupropion but not sertraline. Null findings for sertraline were replicated in the stage 1 sample. ConclusionsPretreatment reward sensitivity and frontostriatal connectivity may identify patients likely to benefit from bupropion following selective serotonin reuptake inhibitor failures. Results call for a prospective replication based on these biomarkers to advance clinical care.

Pharmacotherapy for posttraumatic stress disorder at a Veterans Affairs facility.

Results of a study of psychotropic prescribing patterns in a Veterans Affairs (VA) population with posttraumatic stress disorder (PTSD) are presented. VA prescription records were reviewed to identify veterans with PTSD at a large VA healthcare center and evaluate their medication regimens for conformance with a VA practice guideline that calls for the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) as first-line therapies for PTSD; the VA guideline does not recommend second-generation antipsychotics (SGAs) and benzodiazepines for PTSD symptom control. The primary objective was to determine if veterans with PTSD who were receiving an SGA had first received SSRI or SNRI therapy in accordance with VA recommendations. Among 308 veterans who met the inclusion criteria, the average number of SSRI or SNRI agents prescribed prior to initiation of SGA therapy was 0.88. Only 19.8% of patients (n = 61) had been prescribed 2 SSRI or SNRI agents, with 48.4% of patients (n = 149) having received 1 agent. All evaluated courses of SSRI and SNRI therapy prior to SGA initiation were of sufficient duration (range, 5-30 months), and mean adherence rates were >80%. Current or past benzodiazepine use was documented in about 55% of patients (n = 170). SSRIs and SNRIs were under-utilized for the treatment of PTSD at the study site in patients receiving an SGA. The current use of benzodiazepines in these patients was lower than a reported national average for VA patients.

Systematic Review and Meta-Analysis: Early Treatment Responses of Selective Serotonin Reuptake Inhibitors in Pediatric Major Depressive Disorder

Selective serotonin reuptake inhibitors (SSRIs) are the first-line pharmacological treatment for pediatric major depressive disorder (MDD). We conducted a meta-analysis to examine the following: the time-course of response to SSRIs in pediatric depression; whether higher doses of SSRIs are associated with an improved response in pediatric depression; differences in efficacy between SSRI agents; and whether the time-course and magnitude of response to SSRIs is different in pediatric and adult patients with MDD. We searched PubMed and CENTRAL for randomized controlled trials comparing SSRIs to placebo for the treatment of pediatric MDD. We extracted weekly symptom data from trials to characterize the trajectory of pharmacological response to SSRIs. Pooled estimates of treatment effect were calculated based on standardized mean differences between treatment and placebo groups. The meta-analysis included 13 pediatric MDD trials with a total of 3,004 patients. A logarithmic model indicating that the greatest benefits of SSRIs occurred early in treatment best fit the longitudinal data (log[week]= 0.10, 95% CI= 0.06-0.15, p< .0001). There were no significant differences based on maximum SSRI dose or between particular SSRI agents. SSRIs were demonstrated to have a smaller benefit in pediatric compared to adult MDD. Treatment gains in pediatric MDD are greatest early in treatment and are, on average, minimal after 4 weeks of SSRI pharmacotherapy in pediatric MDD. Further research is needed using individual patient data to examine the power of early SSRI response (e.g., 2-4 weeks) to predict outcomes in short-term pharmacological trials.

Breast ecchymosis: Unusual complication of an antidepressant agent

INTRODUCTIONFluoxetine is a selective serotonin reuptake inhibitor (SSRI) that is safely used for treatment of psychosomatic disorders. Despite being associated with a low side effect profile, it has been reported to cause hematological side effects including vaginal bleeding, epistaxis, purpura, hematuria, intracranial bleeding, and rectal bleeding. Isolated breast ecchymosis is one of exceedingly rare SSRI-induced hematological abnormalities. PRESENTATION OF CASEIn this case study, we report a case of left breast ecchymosis in a 75-year-old woman that developed in conjunction with use of the SSRI fluoxetine. DISCUSSIONThe use of SSRIs has surged over the past decades due to increased diagnosis and focus on clinical management of depression and anxiety disorders, especially in developed nations. The low side effect profiles of the eight currently marketed SSRI agents has further promoted their use in the general population. While the most commonly reported side effects are mild and relatively tolerable, a risk of SSRI-related abnormal bleeding exists and may represent a life-threatening side effect. The most frequent SSRI-related bleeding manifestation is ecchymosis, but cases of isolated breast ecchymosis are exceedingly rare and to date only one report of SSRI-induced breast ecchymosis is included in the publicly available literature. CONCLUSIONThree factors may have played a role in lack of reports describing SSRI-induced breast ecchymosis in literature. First, SSRIs indeed very seldom cause breast ecchymosis; second, physicians are not aware of such a causal relationship; and third, physicians find this side effect not worth to publish.

Response to antidepressants in major depressive disorder with melancholic features: the CRESCEND study

This study aimed to determine whether major depressive disorders with melancholic and without melancholic features differ with respect to their responses to treatment with antidepressants. From a nationwide sample of 18 hospitals in South Korea, 559 presenting patients with major depressive disorder were recruited. The DSM-IV based Structured Clinical Interview was administered for confirmatory diagnoses and depression subtypes with/without melancholic features. After baseline evaluation, they received naturalistic clinician-determined antidepressant interventions. Assessment scales for evaluating depression (HAMD), anxiety (HAMA), global severity (CGI-s), and functioning (SOFAS) were administered at baseline and re-evaluated at 1, 2, 4, 8, and 12 weeks later. At baseline, the 243 (43.5%) participants with melancholic features were more likely to have a previous history of depression, and had higher HAMA and lower SOFAS scores. After adjustment for baseline status, participants with melancholic features were more likely to achieve and to experience shorter times to CGI-s remission and associated with an enhanced global symptomatic remission with any antidepressant treatment. They were more likely to achieve and to experience shorter times to CGI-s remission and this difference was strongest in those receiving selective serotonin reuptake inhibitor (SSRI) antidepressants treatment. The study was observational, and the treatment modality was naturalistic. These findings suggest a faster and more evident global response to pharmacotherapy in melancholia compared to other depressive syndromes, particularly where SSRI agents are used.

Psychological Distress and Depression in Patients with Chronic Kidney Disease

Depressive disorders are 1.5-4 times more prevalent in medically ill patients than in the general population. Mood disorders can be regarded as the final common pathway developing from the interaction among multiple pathophysiological, psychological, and socioeconomic stressors that chronic illness imposes on the individual. Symptoms of clinical depression affect approximately 25% patients on hemodialysis and can be associated with low quality of life and increased mortality. The epidemiology of depressive disorders is less well studied in the renal transplant population. However, depression is a risk factor for poor outcomes, such as graft failure and death after renal transplantation. A high prevalence of severe psychological distress in patients with advanced CKD and its impact on CKD outcomes call for screening and intervention integrated in routine renal care. Preliminary data indicate that some of the selective serotonin reuptake inhibitor agents and time-limited, manualized, structured psychotherapies can be safe and effective for treating depression in this population.

Interaction between serotonin reuptake inhibitors, 5-HT3 antagonists, and NK1 antagonists in cancer patients receiving highly emetogenic chemotherapy: a case–control study

Previous reports suggested that selective serotonin reuptake inhibitors (SSRI) could decrease the activity of 5-hydroxytryptamine type 3 (5-HT3) antagonists against acute chemotherapy-induced nausea and vomiting (CINV), possibly through serotonin accumulation for 5-HT3 receptors. Chemonaive cancer patients receiving SSRI and antiemetic agents, including the 5-HT3 antagonist ondansetron and the neurokinin 1 (NK1) antagonist aprepitant for highly emetogenic chemotherapy (etoposide-platinum), were matched to control patients for the following variables: age, gender, primary tumor, past history of gestational emesis, chronic intake of benzodiazepines and/or corticosteroids, chronic alcohol intake, and aprepitant use. The primary evaluation criterion was the occurrence of acute vomiting during the first two cycles of treatment. Forty-four patients were eligible for this analysis. The proportion of patients, who experienced at least one episode of grade ≥ 1 acute vomiting in patients receiving SSRI, compared to patients who did not, was significantly higher (59.1 vs. 22.7%, respectively, p = 0.03, odds ratio 4.72, 95% confidence interval 1.13-22.88). Grade ≥ 2 acute vomiting was also significantly more frequent in patients receiving SSRI, even after the implementation of aprepitant to antiemetic prophylaxis (41.2 vs. 5.9%, p = 0.04). Our findings reinforce the hypothesis that SSRI decrease the antiemetic activity of the 5-HT3 serotonin antagonist ondansetron, resulting in higher rates of acute vomiting in cancer patients despite adequate antiemetic prophylaxis. Adding the NK1 antagonist aprepitant do not counterbalance the deleterious effect of SSRI, probably due to the synergistic effects of SSRI and NK1 antagonists on serotonin transmission.

P.4.e.001 Relationship of clomipramine levels and OCD symptoms in adult patients

We conducted a meta-analysis to examine the following: the time course of response to selective serotonin reuptake inhibitors (SSRIs) and clomipramine in pediatric obsessive-compulsive disorder (OCD); whether higher doses of SSRIs are associated with an improved response in pediatric OCD; differences in efficacy among SSRI agents; differences in efficacy between SSRIs and clomipramine; and whether the time course and magnitude of response to SSRIs are different in pediatric and adult patients with OCD.We searched PubMed and CENTRAL for randomized controlled trials comparing SSRIs (or clomipramine) to placebo for the treatment of pediatric OCD and using the Children’s Yale−Brown Obsessive-Compulsive Scale as an outcome. We extracted weekly symptom data from trials to characterize the trajectory of pharmacological response to SSRIs. Pooled estimates of treatment effect were calculated based on weighted mean differences between the treatment and placebo groups.Nine trials involving 801 children with OCD were included in this meta-analysis. A logarithmic model indicating that the greatest benefits occurred early in treatment best fit the longitudinal data for both clomipramine and SSRIs. Clomipramine was associated with a greater measured benefit compared to placebo than SSRIs. There was no evidence for a relationship between SSRI dosing and treatment effect, although data were limited. Adults and children with OCD demonstrated a similar degree and time course of response to SSRIs in OCD.These results suggest that the greatest incremental treatment gains in pediatric OCD occur early in SSRI treatment (similar to adults with OCD and children and adults with major depression).

Semen Parameters are Unrelated to BMI But Vary With SSRI Use and Prior Urological Surgery

Male infertility affects approximately 6% of reproductive-aged men. It has been suggested that overweight men or men with obese body mass index (BMI) experience prolonged time to pregnancy, though the influence of male BMI on fertility remains understudied. We hypothesized that BMI is inversely correlated with fertility, manifested by reduced sperm concentration, motility, and morphology. Males of age 18 to 50 with semen analyses and self-reported BMI were included (n = 530). Patient parameters analyzed included age, BMI, smoking, urological, and fertility history. Leutinizing hormone (LH), Follicle-stimulating hormone, testosterone, steroid hormone-binding globulin (SHBG) and free androgen index (FAI) levels (n = 55), and selective serotonin reuptake inhibitor (SSRI) use (n = 12) were also measured. The men in this study had a mean BMI of 28.2 ± 4.9 kg/m(2) (range = 15-60), which is considered overweight, and a mean semen concentration of 55.4 ± 46.8 million/mL, which is in normal range, according to WHO standard. No consistent relationship was observed between increasing BMI and sperm concentration, motility, or morphology, although the testosterone levels trended downward with increasing BMI; there was a suggestion for decreased sperm concentration in current smokers. Men treated with combination SSRI and other psychotropic agent therapy (n = 12) had significantly reduced sperm motility (P = .009). Not unexpectedly, prior urological surgery (n = 77) was associated with lower sperm concentration (P = .0001) and morphology (P = .0008). When in vitro fertilization-embryo transfer (IVF-ET) was used as a treatment modality (n = 121), male BMI was not a significant predictor of clinical pregnancy (P = .06). In our study, we did not observe a significant association between male BMI and sperm concentration, motility or morphology, or clinical pregnancy following IVF-ET. Significantly, SSRI use may affect sperm parameters negatively.

Selective serotonin reuptake inhibitor exposure during early pregnancy and the risk of birth defects

To assess the methodological value of studies that signaled one or more selective serotonin reuptake inhibitors (SSRIs) as teratogenic agents. Medical literature, published in English (1980-November 2010), was searched using MEDLINE/PubMed, TOXNET, EMBASE, and The Cochrane Library to identify all articles, reporting primary data that suggested any increased rate of congenital malformations following prenatal exposure to SSRIs as a group or single SSRI agents. Reviewed studies showed some severe methodological limitations, such as data coming from retrospective studies and incomplete information available with reference to timing of exposure and dosages. Further, data continue to be extrapolated from automated databases that do not declare whether the women reported actually used the prescribed medication. Further, it should be noted the distinct lack of research analysis available with reference to the potential impact of non-iatrogenic confounders on pregnancy. In light of such considerations, the hypothesized teratogenicity of SSRIs remains undemonstrated. Hence, further, well-designed research is needed to differentiate definitively the detrimental impact of depression on pregnancy outcomes from potential iatrogenic events.

Use of SSRIs in Pregnancy: Neonatal Implications

ing pregnancy, and (4) implications of drug transfer to the infant via breast milk. Using a case study approach and a systematic appraisal of the risks-benefits-alternative model, this article will consider the scientific evidence surrounding fetal and neonatal exposure to SSRIs in the perinatal period and via breast milk, Depressed mood in pregnancy and the postpartum period is commonly acknowledged as a risk factor for both mother and baby. Selective serotonin reuptake inhibitors (SSRIs) have increasingly been used to treat perinatal mood disorders; however, new risks related to the use of specific SSRI agents have been documented. Research into adverse effects of SSRI use in pregnancy has focused primarily on four areas: (1) congenital defects stemming from first trimester exposure, (2) neonatal behavioral effects secondary to third trimester exposure, (3) maternal and fetal outcomes resulting from suspending antidepressant therapy durDepressed mood

The Risk of Postpartum Hemorrhage With Selective Serotonin Reuptake Inhibitors and Other Antidepressants

Limited evidence suggests that selective serotonin reuptake inhibitor (SSRI) antidepressants can hinder platelet aggregation and can increase the risk of hemorrhage. Because antenatal depression is common and is often treated with antidepressants, we sought to determine if exposure to SSRI antidepressants in late pregnancy is associated with an increased risk of postpartum hemorrhage compared with non-SSRI antidepressants. This was a population-based nested case-control study of women aged 16 to 45 years in Ontario, Canada, who received government-funded prescription coverage within 2 years before delivery. We identified case patients with postpartum hemorrhage and matched controls (1:10) without postpartum hemorrhage from the same cohort. Controls were matched to cases on age, mode of delivery, parity, and calendar time. We linked prescription claims data to hospital and physician records for the study period (January 1999 to March 2005). Exclusion criteria included drugs and medical conditions that predispose to hemorrhage, and receipt of multiple antidepressants in the 6 months preceding delivery. Antidepressant drug exposure was classified as SSRI or other agents within 90 days before delivery. There were 2460 postpartum hemorrhage cases and 23,943 matched controls. The adjusted odds ratio for the association between postpartum hemorrhage and exposure to SSRIs within 90 days before index date was 1.30 (95% confidence interval, 0.98-1.72) as compared with 1.12 (95% confidence interval, 0.62-2.01) for non-SSRIs. Selective serotonin reuptake inhibitors confer no disproportionate risk of postpartum hemorrhage at the time of delivery compared with non-SSRI antidepressants. This information may help guide decisions regarding pharmacotherapy for depression during pregnancy.

Risks of Suicide and Poisoning Among Elderly Patients Prescribed Selective Serotonin Reuptake Inhibitors

Treatment with selective serotonin reuptake inhibitors (SSRIs) has been associated with increased suicide risk. Risks of suicide death and of poisoning were compared during periods of SSRI treatment versus periods without any antidepressant treatment among elderly patients. In this retrospective cohort study, records from the Quebec Health Care Fund and Vital Statistics databases were obtained for patients 65 years and older who had filled a prescription for an SSRI between January 1998 and December 2004. Patients were followed from the filling date of the first SSRI prescription during the study period until death, the end of the first period extending for at least 365 days with no antidepressant supply, or December 31, 2004, whichever occurred first. The cohort included 128,229 patients (mean age = 75.4 years), 70% of whom were women. Numbers of suicide deaths (crude rate/100,000 patient-years) were 37 (23) during SSRI use, 16 (51) during other antidepressant use, 5 (54) during use of both an SSRI and another anti-depressant, and 29 (29) during no antidepressant use. The adjusted risk of suicide death (Cox regression model with time-dependent exposure) was not higher during SSRI use versus nonuse (hazard ratio [95% CI]): any SSRI = 0.64 (0.38 to 1.07), paroxetine = 0.71 (0.37 to 1.35), citalopram = 1.16 (0.59 to 2.25), and sertraline = 0.38 (0.16 to 0.93). The adjusted hazard ratio (95% CI) of poisoning was higher during SSRI use versus nonuse (1.16 [1.07 to 1.25]) and varied between SSRI agents from 0.93 (0.74 to 1.16) for fluoxetine to 1.45 (1.23 to 1.71) for fluvoxamine. Among elderly patients dispensed SSRIs, the risk of suicide death was not higher during periods of SSRI use compared to when antidepressants were not being used.

Clinical impact of selective serotonin reuptake inhibitors therapy with bleeding risks

The selective serotonin reuptake inhibitors (SSRIs) are extensively used for the treatment of multiple psychiatric conditions. In vitro and ex vivo data with these agents indicate they may have varying degrees of antiplatelet activity via multiple receptors. Reports of bleeding in patients receiving SSRIs appeared soon after their introduction. A review of the literature suggests SSRI therapy may increase the risk of bleeding especially with concomitant aspirin or nonsteroidal anti-inflammatory agents. Clinicians should exercise caution when prescribing these agents in high risk patients and maintain awareness of the potential contribution of SSRIs to unexplained bleeding episodes.

Differences in compliance patterns across the selective serotonin reuptake inhibitors (SSRIs)

ABSTRACTObjective: To evaluate differential compliance rates between immediate-release (IR) selective serotonin reuptake inhibitors (SSRI) and a controlled-release (CR) SSRI in patients initiating SSRI therapy.Methods: A retrospective analysis of patients initiating treatment with SSRIs identified in the IHCIS National Managed Care Database between July 2001 and December 2002 was conducted. Logistic regression models were used to assess differences in 6‐month compliance rates, controlling for age, gender, utilization of mental health specialty care services, titration rates, diagnoses, and comorbidities. Compliance was defined as having a minimum medication possession ratio of 80% over a 180-day period without evidence of a 15‐day gap prior to 90 days of therapy.Results: There were 116 090 patients included in the study, with approximately 4% receiving a CR SSRI and 96% receiving IR SSRIs. Approximately 25% of patients had a diagnosis for depression, 16% had a diagnosis for anxiety, and 13% had a diagnosis for both anxiety and depression. Overall, 54.2% were noncompliant with therapy, while 30.2% of patients were compliant with therapy, and 15.7% had evidence of a therapy change. After controlling for baseline covariates, patients initiating IR SSRIs were 14% less likely to be compliant compared to those initiating paroxetine CR ( p < 0.0001). Patients initiating on paroxetine IR were least likely to be compliant (odds ratio [OR] 0.788; p < 0.0001), followed by escitalopram (OR 0.850; p = 0.0179), sertraline (OR 0.877; p = 0.0005), citalopram (0.909; p = 0.0114), and fluoxetine (OR 0.916; p = 0.0250).Conclusions: Approximately 54% of patients initiating SSRI therapy were noncompliant with SSRI therapy over a 6‐month period, with the lowest level of compliance found in patients receiving IR SSRI agents. Future studies should assess the effect of compliance on economic measures and determine if reductions in resource utilization are found across specific SSRI agents.

Maladie d’Alzheimer, traitement des troubles psychologiques et comportementaux

When psychological and behavioral disorders of Alzheimer's disease appear suddenly, somatic, iatrogenic and reactive or relational psychological causes must be ruled out or treated before concluding that the cause is lesional. Non-pharmacological interventions should be privileged for the prevention and management of behavioral manifestations of mild to moderate intensity: psychological support of the patient (short therapies), training the caregiver, work on daily habits, reorganization of the home, behavioral measures against apathy and especially agitation, rehabilitation strategies, and therapy involving music, light, aromas, etc. Pharmacological therapies are only moderately effective in these disorders. They must be targeted and follow a sequence of prescription that maximizes tolerance and distinguishes treatment of acute and chronic states. Anticholinesterase agents may be useful in this domain to prevent or ease some symptoms (especially apathy). The efficacy of memantine must be confirmed by additional data. Some selective serotonin reuptake inhibitors agents may be useful not only in depression but also anxiety, emotional disturbances, irritability and compulsiveness. Atypical neuroleptics are better tolerated than the classic ones. They are most effective in this context but must be reserved for specific indications and limited in time because of the increased risk of stroke. Other psychotropics (benzodiazepines, carbamates, antiepileptics) should be used cautiously in this context.

The effect of fluvoxamine on ouabain-induced arrhythmia in isolated guinea-pig atria

The effect of fluvoxamine (FLV) a selective serotonin reuptake inhibitor agent was studied on ouabain-induced arrhythmia in spontaneously beating isolated guinea-pig atria. FLV (8–64 μM) caused a dose-dependent decrease in the rate of contractions (7–52%) and in the contractile force (11–57%). Ouabain alone (2 μM) produced arrhythmia at 4.6 min and asystole at 17.4 min. Pre-administration of the atria with FLV (32 μM) significantly increased the time required to produce arrhythmia by ouabain to 14.6 min, prolonged the beating of atria to more than 58.6 min and delayed the occurrence of asystolia. The pattern of contractile force induced by FLV + ouabain was more regular than that produced by ouabain alone. These findings indicate that FLV produces direct cardiac action, probably due to the inhibition of cardiac Na + and Ca 2+ channels. Our results suggest that FLV may reduce the membrane conduction through inhibition of ionic channels which decrease ouabain-induced arrhythmia.

Paroxetine in panic disorder: clinical management and long-term follow-up

Panic disorder is one of the most common anxiety disorders and has a lifetime prevalence of 3–5%. Panic attacks can begin at any age, but commonly have their onset in early adulthood between the ages of 20 and 40 years. Naturalistic data has shown that panic disorder has a chronic and relapsing course. Panic disorder is reported to be associated with an increased risk of suicidal behavior and comorbid psychiatric diagnoses such as depression and substance abuse. Currently, recommended treatment modalities for panic disorder include the use of antidepressant pharmacotherapy and/or cognitive behavioral therapy. Paroxetine is unique among the selective serotonin reuptake inhibitors since, in addition to its effect on the CNS serotonergic neurotransmission, it also has mild noradrenergic properties demonstrated to be effective in the treatment of anxiety disorders and depression. Paroxetine treatment has the potential to cause weight gain and sexual dysfunction, primarily anorgasmia and ejaculatory dysfunction for the long term. In the short-term, treatment causes nausea, gastrointestinal disturbances, irritability, headaches and eating and sleeping difficulties. Paroxetine is an example of an selective serotonin reuptake inhibitor agent, which has been well studied in the treatment of panic disorder and is efficacious and well-tolerated. Paroxetine pharmacotherapy has been recommended to be continued for 1 year as specified in the treatment guidelines set by the American Psychiatric Association in the treatment of panic disorder.