Initiation Of Selective Serotonin Reuptake Inhibitors Research Articles

Comparative Safety of Antidepressants in Adults with CKD.

Depression is prevalent in patients with CKD and is related to poor prognosis. Despite the widespread use of antidepressants in the CKD population, their safety remains unclear. We identified adults with CKD stages G3-5 (eGFR <60 ml/min per 1.73 m 2 not treated with dialysis) and incident depression diagnosis during 2007-2019 from the Stockholm Creatinine Measurements project. Using the target trial emulation framework, we compared the following treatment strategies: ( 1 ) initiating versus not initiating antidepressants, ( 2 ) initiating mirtazapine versus selective serotonin reuptake inhibitors (SSRIs), and ( 3 ) initiating SSRIs with a lower dose versus a standard dose. Of 7798 eligible individuals, 5743 (74%) initiated antidepressant treatment. Compared with noninitiation, initiation of antidepressants was associated with higher hazards of short-term outcomes, including hip fracture (hazard ratio [HR], 1.23; 95% confidence interval [CI], 0.88 to 1.74) and upper gastrointestinal bleeding (HR, 1.38; 95% CI, 0.82 to 2.31), although not statistically significant. Initiation of antidepressants was not associated with long-term outcomes, including all-cause mortality, major adverse cardiovascular event, CKD progression, and suicidal behavior. Compared with SSRIs, initiation of mirtazapine was associated with a lower hazard of upper gastrointestinal bleeding (HR, 0.52; 95% CI, 0.29 to 0.96), but a higher hazard of mortality (HR, 1.11; 95% CI, 1.00 to 1.22). Compared with the standard dose, initiation of SSRIs with a lower dose was associated with nonstatistically significantly lower hazards of upper gastrointestinal bleeding (HR, 0.68; 95% CI, 0.35 to 1.34) and CKD progression (HR, 0.80; 95% CI, 0.63 to 1.02), but a higher hazard of cardiac arrest (HR, 2.34; 95% CI, 1.02 to 5.40). Antidepressant treatment was associated with short-term adverse outcomes but not long-term outcomes in people with CKD and depression.

Selective serotonin reuptake inhibitor use and risk of major bleeding during treatment with vitamin K antagonists: results of a cohort study.

Selective serotonin reuptake inhibitors (SSRIs) may increase the risk of major bleeding by decreasing platelet function or decreasing vitamin K antagonist (VKA) metabolism via cytochrome P450 (CYP) inhibition. To determine whether SSRIs are associated with major bleeding during VKA treatment and investigate the possible mechanisms. In this cohort study, information on SSRI use and bleeding complications was obtained from patient records of VKA initiators between 2006 and 2018 from two anticoagulation clinics. Conditional logistic regression and time-dependent Cox regression were used to estimate the effect of SSRIs on a high INR (≥ 5) within 2 months after SSRI initiation and on major bleeding during the entire period of SSRI use, respectively. SSRI use was stratified for (non-)CYP2C9 inhibitors. 58,918 patients were included, of whom 1504 were SSRI users. SSRI initiation versus non-use was associated with a 2.41-fold (95% confidence interval [CI] 2.01-2.89) increased risk for a high INR, which was 3.14-fold (95%CI 1.33-7.43) among CYP2C9 inhibiting SSRI users. The adjusted hazard ratio of major bleeding was 1.22 (95%CI 0.99-1.50) in all SSRI users and 1.31 (95%CI 0.62-2.72) in CYP2C9 inhibiting SSRI users compared to non-users. SSRI use is associated with an increased risk of high INR and might be associated with major bleeding. The risk of a high INR was slightly more elevated for CYP2C9 inhibiting SSRI users, suggesting there might be a pharmacokinetic interaction (by CYP2C9 inhibition) next to a pharmacodynamic effect of SSRIs on platelet activation.

Norepinephrine reuptake inhibitors and risk of antihypertensive treatment intensification and major adverse cardiovascular events in patients with stable hypertension and depression.

To compare the risk of antihypertensive treatment intensification (TI) and major adverse cardiovascular events (MACE) with the initiation of serotonin norepinephrine reuptake inhibitors compared to selective serotonin reuptake inhibitors (SSRIs) in patients with stable hypertension and depression. Retrospective cohort study. IBM MarketScan® commercial claims database and Medicare Supplemental claims database from 2007 to 2019. Patients aged 18 years or older with stable treated hypertension and depression who newly initiate either serotonin norepinephrine reuptake inhibitors or SSRIs. Serotonin norepinephrine reuptake inhibitors versus SSRIs. The primary outcomes were: (1) TI (first occurrence of antihypertensive regimen augmentation or dose escalation); (2) MACE (first occurrence of stroke or acute myocardial infarction). Baseline risk between the two groups was balanced via 1:1 propensity score (PS) matching. A Cox proportional hazard regression model was used to estimate adjusted hazard ratio (aHR) and 95% confidence intervals (95% CI). After 1:1 PS matching, we included 19,160 patients in the study cohort (mean age: 52 years, 62% females) of which 9580 initiated serotonin norepinephrine reuptake inhibitors and 9580 initiated SSRIs. Patients who initiated serotonin norepinephrine reuptake inhibitors had 15 MACE events (incidence rate per 1000 person-years [IR], 3.9) and 1675 TI events (IR, 540.2), compared with 17 MACE events (IR, 4.0) and 1774 TI events (IR, 518.5) in the SSRI group. The risk of TI (aHR: 1.01, [95% CI: 0.94, 1.08]) and MACE (aHR: 0.98, [95% CI: 0.49, 1.96]) did not differ among patients initiated serotonin norepinephrine reuptake inhibitors versus SSRIs. Among patients with stable hypertension and depression, initiation of serotonin norepinephrine reuptake inhibitors had a similar risk of antihypertensive TI and MACE compared to initiation of SSRIs. Future study with a larger sample size is needed to confirm our findings.

Surveillance of Antidepressant Safety (SADS): Active Signal Detection of Serious Medical Events Following SSRI and SNRI Initiation Using Big Healthcare Data.

IntroductionThe current process for generating evidence in pharmacovigilance has several limitations, which often lead to delays in the evaluation of drug-associated risks.ObjectivesIn this study, we proposed and tested a near real-time epidemiological surveillance system using sequential, cumulative analyses focusing on the detection and preliminary risk quantification of potential safety signals following initiation of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).MethodsWe emulated an active surveillance system in an historical setting by conducting repeated annual cohort studies using nationwide Danish healthcare data (1996–2016). Outcomes were selected from the European Medicines Agency's Designated Medical Event list, summaries of product characteristics, and the literature. We followed patients for a maximum of 6 months from treatment initiation to the event of interest or censoring. We performed Cox regression analyses adjusted for standard sets of covariates. Potential safety signals were visualized using heat maps and cumulative hazard ratio (HR) plots over time.ResultsIn the total study population, 969,667 new users were included and followed for 461,506 person-years. We detected potential safety signals with incidence rates as low as 0.9 per 10,000 person-years. Having eight different exposure drugs and 51 medical events, we identified 31 unique combinations of potential safety signals with a positive association to the event of interest in the exposed group. We proposed that these signals were designated for further evaluation once they appeared in a prospective setting. In total, 21 (67.7%) of these were not present in the current summaries of product characteristics.ConclusionThe study demonstrated the feasibility of performing epidemiological surveillance using sequential, cumulative analyses. Larger populations are needed to evaluate rare events and infrequently used antidepressants.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40264-021-01110-x.

Suicidality and self-injury with selective serotonin reuptake inhibitors in youth: Occurrence, predictors and timing.

ObjectiveMeta‐analyses have established a heightened risk of suicidality for youth treated with selective serotonin reuptake inhibitors (SSRIs). The present study investigates the risk and possible predictors of suicidality and non‐suicidal self‐injury (NSSI) associated with SSRI treatment in a clinical sample of children and adolescents.MethodsAn observational, longitudinal, retrospective study using a within‐subject study design including in‐ and outpatients aged 0–17 years treated with SSRIs. Data were obtained from digital medical records and prescription software.Results N = 365 patients were included (64.1% female), mean (SD) age 14.5 (2.04) years, with primary depression, anxiety or obsessive‐compulsive disorder. No suicides occurred. When comparing the 6‐week period immediately prior to versus following SSRI initiation, the patient proportion with broadly defined suicidality decreased (38.5% vs. 24.2%, p < 0.001) while the proportion with suicide attempts was stable (2.8% vs. 2.8%, p = 1.000). The proportion with NSSI decreased statistically non‐significantly (12.4% vs. 8.4%, p = 0.067). Results from individually standardized observation periods were similar; however, the proportion with suicide attempts decreased statistically non‐significantly and the proportion with NSSI decreased significantly. Suicidality during SSRI treatment was associated with previous suicidality (OR[CI] = 6.0 [2.4–14.8], p < 0.001), depression as indication for SSRI treatment (OR[CI] = 2.1 [1.2–3.7], p = 0.01), female sex (OR[CI] = 2.1 [1.1–4.1], p = 0.02) and previous NSSI (OR[CI] = 2.0 [1.2–3.5], p = 0.01).ConclusionSuicidality was common in youth treated with SSRIs. The patient proportion with overall suicidality decreased, and the proportion with attempted suicide was stable in the weeks following SSRI initiation. Previous suicidality, depression, female sex and previous NSSI are important predictors for suicidality during SSRI treatment in youth.

Selective serotonin reuptake inhibitors and the risk of restless legs syndrome: a symmetry analysis.

Largely based on case series, several drugs have been implicated in drug-induced restless legs syndrome (RLS) including selective serotonin reuptake inhibitors (SSRI). We aimed to assess the association between initiation of SSRIs and RLS in a self-controlled design. We conducted a symmetry analysis, including Danish adults who filled in their first prescription of an SSRI in the period of 1997-2017 and initiated an RLS drug (quinine, ropinirole, pramipexole or rotigotine) 1year prior to or after this date. A symmetrical distribution of prescriptions before and after SSRI initiation is expected if there is no association between SSRI and RLS (a sequence ratio (SR) of 1.0). The symmetry analysis design is robust to confounders that are stable over time. Subgroup analyses were conducted, restricting the population on sex, age, selected diagnoses and concurrent medication. A total of 10,875 patients filled in their first-ever prescription of both an SSRI and an RLS drug within a 1-year interval; 5341 patients filled their prescription of SSRI prior to their prescription of an RLS drug, and 5534 patients redeemed their prescriptions in the opposite order (SR 0.97, 95% CI 0.93-1.00). Restricting the outcome to dopamine agonist initiation revealed a slightly increased sequence ratio (SR 1.34, 95% CI 1.24-1.46), which was reduced when adjusting for trends in prescription (adjusted SR 1.21, 95% CI 1.12-1.32). Restricting the outcome to quinine initiation showed no association. We found no association between the initiation of an SSRI and the development of RLS assessed by the prescription of an RLS drug.

Clinician compliance to recommendations regarding the risk of suicidality with selective serotonin reuptake inhibitors in the treatment of children and adolescents

Meta-analyses of randomized-controlled trials have established a heightened risk of suicidality for children and adolescents treated with selective serotonin reuptake inhibitors (SSRIs). The present study examined to what extent daily clinical practice complied with specific recommendations regarding the risk of suicidality when treating children and adolescents with SSRIs. All in- and outpatients aged 0–17 years at the Child and Adolescent Mental Health Services, Capital Region of Denmark with a prescription for SSRI on January 1st, 2016 were identified. Data were obtained for n = 365 patients regarding the level of clinician compliance to deliver pre-consent information about adverse effects, monitor for suicidality, and provide non-pharmacological interventions. 81.7% (n = 298) of patients received pre-consent information about adverse effects. 67.7% (n = 247) were monitored for suicidality within 6 weeks after SSRI initiation. Children (0–13 years) were less likely to be monitored for suicidality compared to adolescents (14–17 years) (49.6% vs. 77.5%, p < 0.001). Patients with depression as indication for SSRI treatment were more likely to be monitored for suicidality than patients with other indications (OR = 3.4, p = 0,002) and more likely to receive information specifically about suicidality (34.7% vs. 19.7%, p = 0.002). Respectively, 89.3% (n = 326) and 93.4% (n = 341) of all SSRI-treated patients were treated with non-pharmacological interventions prior to and in parallel with SSRI treatment. For the majority of cases, treatment of children and adolescents with SSRI complied with recommendations from clinical guidelines. However, patients of younger age and/or with indications for SSRIs other than depression were less likely to be managed according to recommendations.

Effect of the selective serotonin reuptake inhibitors over coagulation in patients with depressive disorders – a systematic review and retrospective analysis

Several problems related to coagulation dysfunctions induced by selective serotonin reuptake inhibitors (SSRIs) were reported in literature, as serotonin is widely distributed in the human organism and it has significant contribution in various vascular and hematologic regulatory mechanisms. First, a systematic review has integrated main results from the field of SSRIs and anticoagulants pharmacologic interactions. Secondly, a retrospective analysis was performed, based on the medical charts of hospitalized patients diagnosed with SSRI-treated depressive disorders, who also received concomitant anticoagulant treatment with acenocoumarol. Platelet count, prothrombin time, activated partial thromboplastin time, and bleeding time were monitored during hospitalization and their values before and after SSRI initiation treatment were compared.

Depression, depressive symptoms and treatments in women who have recently given birth: UK cohort study

ObjectivesTo investigate how depression is recognised in the year after child birth and treatment given in clinical practice.DesignCohort study based on UK primary care electronic health records.SettingPrimary care.ParticipantsWomen who have...

Examining Parental Medication Adherence as a Predictor of Child Medication Adherence in Pediatric Anxiety Disorders.

Selective serotonin reuptake inhibitors (SSRIs) are the recommended first-line pharmacotherapy for pediatric anxiety disorders but adherence remains difficult to predict. To estimate SSRI adherence in children with anxiety disorders and determine if prior parental medication adherence is predictive of child high SSRI adherence. We identified children (3-17 y) initiating SSRI treatment after an anxiety disorder diagnosis in a commercial claims database (2005-2014). We evaluated parent SSRI, statin, and antihypertensive adherence [6-mo proportion days covered (PDC), high adherence=PDC≥0.80] in the year before child SSRI initiation. We estimated risk differences (RD) of child high SSRI adherence (6-mo PDC) stratified by parent adherence and multivariable risk ratios using modified Poisson regression. We estimated change in c-statistic and risk reclassification when adding parent-level covariates with child-level covariates to predict child adherence. In 70,979 children with an anxiety disorder (59%=female, 14=median age), the mean 6-month SSRI PDC was 0.72, with variation by anxiety disorder. Overall 64% of children had high adherence if their parent had high SSRI adherence versus 53% of children with parents with low SSRI adherence (RD, 12%; multivariable risk ratios, 1.17; 95% confidence interval, 1.14-1.20). Findings were similar for parent statin (RD=10%) and antihypertensive adherence (RD=8%) and when stratified by child age and parent sex. There was minor improvement in risk reclassification and the c-statistic after adding parent adherence and parent-level covariates. Parental medication adherence could help providers identify children at risk of nonadherence to inform the treatment decision, reduce unnecessary medication switches, and lead to broader effective interventions.

Antipsychotic discontinuation after the initiation of selective serotonin reuptake inhibitors therapy for the treatment of behavioral and psychological symptoms associated with dementia.

Introduction:Antipsychotics are used off label to treat behavioral and psychological symptoms of dementia (BPSD). Due to the emerging data of selective serotonin reuptake inhibitors (SSRIs) for treatment of BPSD, clinicians may choose to use this medication class instead of antipsychotics when pharmacologic therapy is necessary. The objective of this study was to evaluate the prevalence of antipsychotic discontinuation 6 months after SSRI initiation for the treatment of BPSD.Methods:Patients with Alzheimer dementia who were prescribed an antipsychotic and later prescribed an SSRI for BPSD during January 1, 2009, through December 30, 2014, were studied. Exclusion criteria included (1) a dementia diagnosis besides Alzheimer; (2) scheduled benzodiazepines, mood stabilizers, or non-SSRI antidepressant use during the study period; (3) diagnoses of bipolar or psychotic disorders; and (4) diagnosis of delirium during the study period. Patients' age, sex, race, and functional assessment of staging for Alzheimer disease scores were collected. The names, doses, and stop dates of SSRIs and antipsychotics were also recorded.Results:Thirty-six patients were included in the analyses. Overall, antipsychotic use was reduced in 11 patients (30.6%). Ten patients (27.8%) discontinued the antipsychotic, and 1 additional patient had a reduction in dose. When comparing specific SSRIs, 8 (72%) responders were prescribed citalopram, and 15 (60%) nonresponders were prescribed sertraline.Discussion:Approximately 30% of patients with Alzheimer dementia who were prescribed antipsychotics for BPSD were able to discontinue the medication or had a dose reduction after starting SSRI therapy. Most SSRI responders were prescribed citalopram.

Pharmacy Practice: Exploring the Relationship between SSRIs and Sodium Levels in an Older Adult Population

I was asked to examine the presence of hyponatremia (&lt;130 mEq/L) in older patients (&gt;65 years) taking Selective Serotonin Reuptake Inhibitors (SSRIs) at Moses Cone Hospital. The presence of hyponatremia in older patients using SSRIs indicates potentially inappropriate use according to the STOPP (Screening Tool of Older Persons’ Potentially Inappropriate Prescriptions) and START (Screening Tool to Alert Doctors to Right Treatment) criteria6. This study was done to assess possible risk factors for potentially inappropriate use of SSRIs by older patients at Moses Cone Hospital. Data collected included the patient’s sex, age, sodium level, and the date the sodium level was drawn. Data also included the specific SSRI and the starting date for the SSRI. The study showed no relationship between age, sex, SSRI prescribed and hyponatremia. However, patients that were prescribed an SSRI for less than a year were more at risk for hyponatremia. Therefore, in order to minimize the risk of hyponatremia, additional monitoring may need to be added at SSRI initiation, three months, six months, and one year, especially in patients with other medications that may lower sodium levels.&#x0D; Conflict of Interest&#x0D; We declare no conflicts of interest or financial interests that the authors or members of their immediate families have in any product or service discussed in the manuscript, including grants (pending or received), employment, gifts, stock holdings or options, honoraria, consultancies, expert testimony, patents and royalties.&#x0D; &#x0D; Type: Student Project

Initiation and duration of selective serotonin reuptake inhibitor prescribing over time: UK cohort study

Recent media reports have focused on the large increase in antidepressants dispensed in England. We investigated this, focusing on selective serotonin reuptake inhibitors (SSRIs). To examine the rate of initiation of SSRIs over time and changes over time in the duration of prescribing episodes. We estimated initiation and duration of SSRI prescribing from 7 025 802 individuals aged over 18 years and registered with a general practice that contributed data to The Health Improvement Network. Rates of SSRI initiation increased from 1.03 per 100 person-years in 1995 to 2.15 in 2001, but remained stable from then to 2012. The median duration of prescribing episodes increased from 112 to 169 days for episodes starting in 1995 to 2010. Despite media reports describing an increasing rate of antidepressant prescribing, SSRI initiation rates have stabilised since 2001. However, our results suggest that individuals who take SSRIs are receiving treatment for longer.

Kleptomania: Beyond serotonin

Sir, Kleptomania has been described as an inability to refrain from the urge to steal things for reasons other than personal use or financial gain. Decades of research show that both dopamine and serotonin are the primary neurotransmitters involved in the pathogenesis and management of kleptomania, respectively. Selective serotonin reuptake inhibitors (SSRIs) have been used as first-line agents for treating kleptomania. On the contrary, cases of kleptomania had been paradoxically induced in three adults who were started on SSRIs for depression.[1] A recent Indian paper also reports a similar manifestation while on fluvoxamine treatment for obsessive compulsive disorder.[2] Restlessness and impulsivity have been recognized as symptoms of behavioral activation during initiation of treatment with SSRIs. Emergence of kleptomania post SSRI treatment may be partly explained by the same phenomenon in which there could be effective depletion of synaptic serotonin post acute administration of SSRIs through serotonin-mediated action on its auto-receptor. While the role of serotonin is murky, the role of dopamine is increasingly getting clearer especially in neurological disorders. Kleptomania is seen as an emergent side effect of the use of dopamine agonists in Parkinson's disease (PD). Other impulse control disorders (ICDs) like pathological gambling, compulsive shopping, compulsive eating and hypersexuality have also been reported with the use of dopamine agonists. This phenomenon is explained by the overdose theory.[3] In PD, ventral striatal dopamine is preserved relative to dorsal striatal activity; thus, dopaminergic treatment titrated to alleviate motor dorsal striatal deficiencies may result in an “over-dosing” in ventral cortico-striatal cognitive and limbic pathways. And as such there is preliminary evidence for the benefit of atypical antipsychotics for treating impulse regulation disorders.[4] At the same time, serotonergic and dopaminergic systems are not mutually exclusive. Could an alteration in dopamine levels post SSRI initiation explain the emergence of kleptomania in rare cases? SSRIs are known to sensitize dopamine (D2) receptors.[5] On the other hand, could the apparent effectiveness of SSRIs in kleptomania be because of their dopaminergic modulation rather than their primary effect on the serotonergic system? Kleptomania shares certain distinct features with substance use disorders, unlike other impulse control disorders like intermittent explosive disorder. This possible association between the two has resulted in naltrexone being tried as a treatment strategy for kleptomania with favorable results.[6] Further supportive evidence can be obtained from the rare finding of new onset alcohol dependence linked to treatment with SSRI.[7] This intriguing phenomenon can be considered similar to the earlier mentioned reports of emergence of kleptomania after taking SSRIs. Probably the mechanism, although still speculative, may be similar in both phenomena. So along with the erstwhile serotonin and dopamine, treatment of kleptomania is further complicated with the involvement of opioid and glutamatergic system.[8] Kleptomania is often been found comorbid with other psychiatric disorders including depression, addiction and personality disorders. Various structural brain lesions have been associated with kleptomania including head trauma.[9] Decreased white matter microstructural integrity in the inferior frontal brain region has also been identified in patients with kleptomania.[10] Functional anatomy of impulse control disorders including kleptomania has recently been reviewed.[11] While medications that affect the serotonergic system have been most widely studied for the treatment of kleptomania, their clinical effects have been modest or inconsistent or even paradoxical. Medications that affect dopaminergic neurotransmission have received less research attention. Kleptomania is the final common manifestation of various underlying pathogenic mechanisms which calls for rationalization of treatment based on co-morbid symptoms and personality traits rather than blanket use of one agent. Extension of this suggestion to other impulse control disorders requires renewed research interest and further elaboration. Developments in neurobiology and pharmaco-genetics, coupled with newer pharmacological models involving the opioid and glutamate systems will surely further our understanding of the pathophysiology and pharmacotherapy of kleptomania.

Risk of Medication‐Associated Initiation of Oxybutynin in Elderly Men and Women

To determine whether there is greater risk of initiation of oxybutynin to treat urinary incontinence (UI) after initiation of medicines reported to be associated with UI. Prescription sequence symmetry analysis (PSSA). Administrative claims data from the Australian Government Department of Veterans' Affairs. Individuals who initiated oxybutynin and a medicine reported to be associated with UI in a 12-month period. Between January 1, 2001, and December 31, 2011, the distribution of incident dispensing of medicines reported to be associated with UI (prazosin, diuretics, calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), hormone replacement therapy (HRT), opioid analgesics, anticonvulsants, levodopa, antipsychotics, sedatives, selective serotonin reuptake inhibitors (SSRIs), venlafaxine, anticholinesterases) was assessed before and after incident dispensing of oxybutynin (to treat UI). Crude and adjusted sequence ratios (ASRs) with 95% confidence intervals (CIs) were calculated. Significant associations between initiation of CCBs, ACEIs, ARBs, and hypnotic-sedatives and subsequent initiation of oxybutynin were found. ASRs ranged from 1.28 (95% CI = 1.19-1.39) for ACEIs to 1.59 (95% CI = 1.29-1.96) for verapamil. In women, there was greater risk of initiation of oxybutynin after prazosin (ASR = 1.84, 95% CI = 1.29-2.63) and HRT (ASR = 1.54, 95% CI = 1.42-1.67) initiation. PSSA showed no significant association with initiation of opioids, anticonvulsants, levodopa, SSRIs, venlafaxine, or anticholinesterases and subsequent initiation of oxybutynin. This study highlights the potential for initiation of commonly used medicines to be associated with subsequent initiation of oxybutynin to treat UI. Greater awareness of the potential for medicines to contribute to UI is required.

An Association between Initiation of Selective Serotonin Reuptake Inhibitors and Suicide - A Nationwide Register-Based Case-Crossover Study

BackgroundTreatment with selective serotonin reuptake inhibitors (SSRI) is one of the most common treatments for depression. It is however not clear whether or not there is an increased short-term suicide risk during initiation with SSRI.MethodsA register-based nationwide case-crossover study including 5,866 suicides, 1,698 women and 4,168 men, from the Death Register 2007-2010 in Sweden. SSRI initiation was defined as a dispensed prescription of SSRI within 28 days prior to the date of suicide with no previous dispensed prescription of SSRI within 4 months prior that prescription. The control period took place one year earlier. Odds ratio (OR) was estimated using conditional logistic regression.ResultDuring the 28 day period prior to suicide 48 women and 138 men were exposed to SSRI initiation (while not being exposed in the control period) and 22 women and 43 men were exposed in the control period (while not being exposed in the case period). The OR for suicide after initiation with SSRI was 2.7 (95% CI: 1.6-44) for women, and 4.3 (95% CI: 3.0-6.1) for men. The highest OR was found 8-11 days after initiation with SSRI 9.7 (95% CI: 3.0-31.7) for women and men combined.ConclusionThe main limitation in this study is confounding by indication, but the descriptive question is however not confounded by indication. Together with plausible biological mechanisms and previous clinical and epidemiological observations our findings, linking initiation of SSRI to increased short-term suicide risk, deserve further attention specifically in the clinical setting.

Cochrane Review: Pharmacotherapy for anxiety disorders in children and adolescents

AbstractBackgroundAnxiety disorders are a potentially disabling group of disorders which are prevalent in childhood and adolescence. The recognition of the early onset of anxiety disorders, and their successful treatment with medication in adults, has led to the growing interest in using medication for paediatric anxiety disorders.ObjectivesTo assess the efficacy and tolerability of medication for treating paediatric anxiety disorders.Search strategyWe searched the Cochrane Depression, Anxiety &amp; Neurosis Group specialised register (CCDANCTR‐Studies), MEDLINE (via PubMed 1966 to August 2008), EMBASE (1966 to August 2008), and PsycINFO (1972 to August 2008). Various electronic registers were searched for unpublished studies. Reference lists of retrieved articles were searched for additional studies.Selection criteriaAll randomised controlled trials (RCTs) of pharmacotherapy in childhood/adolescent anxiety disorders.Data collection and analysisTwo raters independently assessed RCTs for inclusion in the review, collated trial data, and assessed trial quality. Investigators were contacted to obtain missing data. Summary statistics were stratified by medication class, and by medication agent for the selective serotonin reuptake inhibitors (SSRIs). Dichotomous and continuous measures were calculated using a random effects model, heterogeneity was assessed, and subgroup/sensitivity analyses were undertaken.Main results22 short‐term (&lt;= 16 weeks) RCTs were included in the analysis (2519 participants). The majority of the trials assessed the efficacy of the SSRIs (N = 15).Medication and placebo response occurred in 58.1% and 31.5% of patients, respectively (Number of studies (N) = 14, Number needed to treat (NNT) = 4). Medication was more effective than placebo in reducing overall symptom severity in OCD in a post‐hoc comparison (N = 7, Weighted Mean Difference (WMD) = ‐4.45, 95%CI = ‐5.94, ‐2.97, n = 765). Medication was less well tolerated than placebo overall, though the absolute proportion of participants who withdrew due to drug‐related adverse events was low (4.9%).Authors' conclusionsMedication treatments can be effective in paediatric anxiety disorders, acting to reduce core symptoms, and should be considered as part of the treatment of these disorders. The greatest number of trials showing efficacy to date have assessed the SSRIs in treating paediatric OCD.There is no clear evidence to show that any particular class of medication is more effective or better tolerated than any other. As quantitative data was only available for the SSRIs and venlafaxine the routine use of benzodiazepines cannot be recommended, especially given concerns of dependency and treatment ‐related emergent adverse events associated with this class of drugs.Future RCTs could help identify potential clinical moderators of treatment efficacy. Studies of the long‐term efficacy of medication treatment, optimal dosage, as well as direct comparisons of pharmacotherapy and psychotherapy are also warranted.Plain Language SummaryA systematic review and meta‐analysis of randomised controlled trials of medication in treating anxiety disorders in children and adolescentsAnxiety disorders are a potentially disabling group of disorders which frequently occur in childhood and adolescence. Increasing recognition of the early onset of anxiety disorders and of the effectiveness of medication in treating adult anxiety disorders has contributed to a growing interest in the use of medication in treating paediatric patients. This systematic review of randomised controlled trials (RCTs) of pharmacotherapy of anxiety disorders in children and adolescents identified 22 short‐term (&lt;= 16 weeks) randomised controlled trials which were eligible for inclusion (2519 participants). Treatment response was significantly greater after treatment with medication (58.1%) than with placebo (31.5%) in 14 trials. Medication was more effective than placebo in reducing overall symptom severity across all of the anxiety disorders (number of studies (N) = 9). The greatest number of trials were for obsessive compulsive disorder (OCD), for which treatment efficacy in reducing symptom severity was also observed . The greatest number of trials showing efficacy to date have used the selective serotonin reuptake inhibitors (SSRIs). No controlled evidence could be found for the effectiveness of benzodiazepines, despite their continued prescription for paediatric anxiety disorders. Medication was less well tolerated than placebo, as indicated by the significant proportion of children and adolescents who dropped out due to adverse effects during the short term trials. Furthermore, while few incidences of suicidal behaviour/ideation in the included trials were attributed to study medication, it is important to be aware of the need for careful monitoring after initiation of SSRIs in treating this population. In conclusion, medication should be considered as part of the treatment of paediatric anxiety disorders over the short‐term. Additional research into the optimal dose and duration of medication treatment, as well as the effects of age on the efficacy and tolerability of medication is warranted.

Selective serotonin reuptake inhibitor use and outcomes in pulmonary arterial hypertension

Background Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary vascular resistance which leads to right ventricular failure. Serotonin and the serotonin transporter play an important role in animal and human studies of PAH. We therefore hypothesized that PAH patients treated with high-affinity selective serotonin reuptake inhibitors (SSRIs) would have a reduced risk of death compared to PAH patients not treated with SSRIs. Methods We performed a retrospective cohort study of 84 consecutive adult PAH patients who underwent initial evaluation from January 1994 to June 2002 at the Pulmonary Hypertension Center of the New York Presbyterian Hospital. Patient–time while receiving high-affinity SSRIs ( K d<1 nmol) (paroxetine, sertraline, or fluoxetine) was considered “exposed”. Patient–time while receiving tricyclic, atypical, or no antidepressants was considered “unexposed”. Results Thirteen of the 84 patients (15%) used high-affinity SSRIs during the study period. Five patients were taking high-affinity SSRIs at baseline and 8 initiated high-affinity SSRIs during the follow-up period. The median time from baseline evaluation until initiation of high-affinity SSRIs was 125 (0–1227) days. The median duration of high-affinity SSRI use was 482 (110–1624) days and the total at-risk time on high-affinity SSRIs was 18.1 person-years. Seventy-nine (94%) patients were treated with warfarin; 38 (45%) received continuous intravenous epoprostenol; 12 (14%) received continuous subcutaneous treprostinil, and 23 (27%) were treated with oral bosentan. The median follow-up was 764 days. Twenty-four patients died and one underwent lung transplantation during the study period. There were no differences in age, gender, diagnosis, hemodynamics, or incidence of acute vasoreactivity between SSRI users and non-users. The risk of death for high-affinity SSRI users was lower but not statistically significantly different from that of non-users (hazard ratio=0.53, 95% CI 0.07 to 3.9, p = 0.53 ). Adjustment for demographics, diagnosis, hemodynamics, or other therapies did not significantly change this result. Conclusions SSRI use was associated with a 50% reduction in the risk of death in a cohort of PAH patients which was not statistically significant. Larger cohort studies may better define this relationship; an adequately powered trial of high-affinity SSRIs in PAH patients may be warranted.