Tolerability Of Selective Serotonin Reuptake Inhibitors Research Articles

TED-trazodone effectiveness in depression: a naturalistic study of the effeciveness of trazodone in extended release formulation compared to SSRIs in patients with a major depressive disorder.

Introduction: Selective serotonin reuptake inhibitors (SSRIs) are the most often used medications to treat major depressive disorder (MDD). Despite their effectiveness in reducing depressive symptoms, several issues are associated with their use in MDD, such as limited improvement of anhedonia, emergence of emotional blunting, induction or exacerbation of insomnia, and sexual dysfunction. Due to its also devoid of the issues related to treatment noted with SSRIs. The aim of this 12-week non-inferiority naturalistic observation was to compare the effectiveness and tolerability of SSRIs and trazodone in extended release (XR) in MDD. Methods: A total of 186 subjects were recruited, of which 92 received trazodone XR and 94 received SSRIs. Patients were allocated to trazodone XR or SSRIs, according to the attending physician based on clinical evaluation. Assessments at baseline and weeks 2, 4, 8, and 12 were conducted to evaluate the severity of depression (Montgomery-Åsberg Depression Rating Scale, clinician- and patient-rated Quick Inventory of Depressive Symptomatology-the primary endpoints of the study), anhedonia (the Snaith-Hamilton Pleasure Scale), anxiety (the Hamilton Anxiety Rating Scale), insomnia (the Athens Insomnia Scale), and therapeutic effectiveness (the Clinical Global Impression Scale). Results: After 12weeks, trazodone XR was more effective than SSRIs in reducing the severity of depression, anxiety, and insomnia. There was a trend for higher effectiveness of in reduction of anhedonia, which became insignificant after controlling the results for the duration of previous psychiatric treatment as a covariate. The proportion of treatment-responsive subjects in the trazodone XR group compared to SSRIs was comparable or higher. The proportion of patients achieving remission was higher in the trazodone XR arm vs. the SSRI arm. Discussion: In summary, the results indicate that trazodone XR is effective in MDD in the "real-world" setting. Its potential superiority over SSRIs in addressing particular symptomatic dimensions should be verified in future studies.

Pediatric Psychopharmacology for Depressive and Anxiety Disorders.

Anxiety and depressive disorders are the most common psychiatric illnesses among children and adolescents. These disorders are associated with impairments in social, family, and educational functioning. This article summarizes the evidence base for psychopharmacologic interventions; the developmental pharmacology of selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs); and pharmacokinetic and pharmacodynamic differences between youths and adults that call for differences in dosage and affect response and tolerability. The authors also review the efficacy and tolerability of SSRIs and SNRIs in children and adolescents with depressive and anxiety disorder diagnoses, as well as data related to duration of therapy and SSRI/SNRI discontinuation in this population. Taken together, the current evidence suggests that SSRIs are the first-line psychopharmacologic intervention for youths with depressive and anxiety disorders, with SNRIs having a more limited role. These medications are safe and well tolerated, although emerging data and developmental pharmacologic concepts may help clinicians to choose from available SSRIs and to improve the efficacy and tolerability of these medications in children and adolescents.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) for the prevention of tension-type headache in adults.

This is an updated version of the Cochrane review published in 2005 on selective serotonin re-uptake inhibitors (SSRIs) for preventing migraine and tension-type headache. The original review has been split in two parts and this review now only regards tension-type headache prevention. Another updated review covers migraine. Tension-type headache is the second most common disorder worldwide and has high social and economic relevance. As serotonin and other neurotransmitters may have a role in pain mechanisms, SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs) have been evaluated for the prevention of tension-type headache. To determine the efficacy and tolerability of SSRIs and SNRIs compared to placebo and other active interventions in the prevention of episodic and chronic tension-type headache in adults. For the original review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2003, Issue 4), MEDLINE (1966 to January 2004), EMBASE (1994 to May 2003), and Headache Quarterly (1990 to 2003). For this update, we revised the original search strategy to reflect the broader type of intervention (SSRIs and SNRIs). We searched CENTRAL (2014, Issue 10) on the Cochrane Library, MEDLINE (1946 to November 2014), EMBASE (1980 to November 2014), and PsycINFO (1987 to November 2014). We also checked the reference lists of retrieved articles and searched trial registries for ongoing trials. We included randomised controlled trials comparing SSRIs or SNRIs with any type of control intervention in participants 18 years and older, of either sex, with tension-type headache. Two authors independently extracted data (headache frequency, index, intensity, and duration; use of symptomatic/analgesic medication; quality of life; and withdrawals) and assessed the risk of bias of trials. The primary outcome is tension-type headache frequency, measured by the number of headache attacks or the number of days with headache per evaluation period. The original review included six studies on tension-type headache. We now include eight studies with a total of 412 participants with chronic forms of tension-type headache. These studies evaluated five SSRIs (citalopram, sertraline, fluoxetine, paroxetine, fluvoxamine) and one SNRI (venlafaxine). The two new studies included in this update are placebo controlled trials, one evaluated sertraline and one venlafaxine. Six studies, already included in the previous version of this review, compared SSRIs to other antidepressants (amitriptyline, desipramine, sulpiride, mianserin). Most of the included studies had methodological and/or reporting shortcomings and lacked adequate power. Follow-up ranged between two and four months.Six studies explored the effect of SSRIs or SNRIs on tension-type headache frequency, the primary endpoint. At eight weeks of follow-up, we found no difference when compared to placebo (two studies, N = 127; mean difference (MD) -0.96, 95% confidence interval (CI) -3.95 to 2.03; I(2)= 0%) or amitriptyline (two studies, N = 152; MD 0.76, 95% CI -2.05 to 3.57; I(2)= 44%).When considering secondary outcomes, SSRIs reduce the symptomatic/analgesic medication use for acute headache attacks compared to placebo (two studies, N = 118; MD -1.87, 95% CI -2.09 to -1.65; I(2)= 0%). However, amitriptyline appeared to reduce the intake of analgesic more efficiently than SSRIs (MD 4.98, 95% CI 1.12 to 8.84; I(2)= 0%). The studies supporting these findings were considered at unclear risk of bias. We found no differences compared to placebo or other antidepressants in headache duration and intensity.SSRIs or SNRI were generally more tolerable than tricyclics. However, the two groups did not differ in terms of number of participants who withdrew due to adverse events or for other reasons (four studies, N = 257; odds ratio (OR) 1.04; 95% CI 0.41 to 2.60; I(2)= 25% and OR 1.55, 95% CI 0.71 to 3.38; I(2)= 0%).We did not find any study comparing SSRIs or SNRIs with pharmacological treatments other than antidepressants (e.g. botulinum toxin) or non-drug therapies (e.g. psycho-behavioural treatments, manual therapy, acupuncture). Since the last version of this review, the new included studies have not added high quality evidence to support the use of SSRIs or venlafaxine (a SNRI) as preventive drugs for tension-type headache. Over two months of treatment, SSRIs or venlafaxine are no more effective than placebo or amitriptyline in reducing headache frequency in patients with chronic tension-type headache. SSRIs seem to be less effective than tricyclic antidepressants in terms of intake of analgesic medications. Tricyclic antidepressants are associated with more adverse events; however, this did not cause a greater number of withdrawals. No reliable information is available at longer follow-up. Our conclusion is that the use of SSRIs and venlafaxine for the prevention of chronic tension-type headache is not supported by evidence.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) for the prevention of migraine in adults.

This is an updated version of the original Cochrane review published in 2005 on selective serotonin reuptake inhibitors (SSRIs) for preventing migraine and tension-type headache. The original review has been split in two parts and this review now only regards migraine prevention. Another updated review is under development to cover tension-type headache.Migraine is a common disorder. The chronic forms are associated with disability and have a high economic impact. In view of discoveries about the role of serotonin and other neurotransmitters in pain mechanisms, selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) have been evaluated for the prevention of migraine. To determine the efficacy and tolerability of SSRIs and SNRIs compared to placebo and other active interventions in the prevention of episodic and chronic migraine in adults. For the original review, we searched MEDLINE (1966 to January 2004), EMBASE (1994 to May 2003), the Cochrane Central Register of Controlled Trials (CENTRAL 2003, Issue 4), and Headache Quarterly (1990 to 2003). For this update, we applied a revised search strategy to reflect the broader type of intervention (SSRIs and SNRIs). We searched CENTRAL (2014, Issue 10), MEDLINE (1946 to November 2014), EMBASE (1980 to November 2014), and PsycINFO (1987 to November 2014). We also checked the reference lists of retrieved articles and searched trial registries for ongoing trials. We included randomised controlled trials comparing SSRIs or SNRIs with any type of control intervention in participants 18 years and older of either sex with migraine. Two authors independently extracted data (migraine frequency, index, intensity, and duration; use of symptomatic/analgesic medication; days off work; quality of life; mood improvement; cost-effectiveness; and adverse events) and assessed the risk of bias of trials. The primary outcome of this updated review is migraine frequency. The original review included eight studies on migraine. Overall, we now include 11 studies on five SSRIs and one SNRI with a total of 585 participants. Six studies were placebo-controlled, four compared a SSRI or SNRI to amitriptyline, and one was a head-to-head comparison (escitalopram versus venlafaxine). Most studies had methodological or reporting shortcomings (or both): all studies were at unclear risk of selection and reporting bias. Follow-up rarely extended beyond three months. The lack of adequate power of most of the studies is also a major concern.Few studies explored the effect of SSRIs or SNRIs on migraine frequency, the primary endpoint. Two studies with unclear reporting compared SSRIs and SNRIs to placebo, suggesting a lack of evidence for a difference. Two studies compared SSRIs or SNRIs versus amitriptyline and found no evidence for a difference in terms of migraine frequency (standardised mean difference (SMD) 0.04, 95% confidence interval (CI) -0.72 to 0.80; I(2) = 72%), or other secondary outcomes such as migraine intensity and duration.SSRIs or SNRIs were generally more tolerable than tricyclics. However, the two groups did not differ in terms of the number of participants who withdrew due to adverse advents or for other reasons (one study, odds ratio (OR) 0.39, 95% CI 0.10 to 1.50 and OR 0.42, 95% CI 0.13 to 1.34).We did not find studies comparing SSRIs or SNRIs with pharmacological treatments other than antidepressants (e.g. antiepileptics and anti-hypertensives). Since the last version of this review, the new included studies have not added high quality evidence to support the use of SSRIs or venlafaxine as preventive drugs for migraine. There is no evidence to consider SSRIs or venlafaxine as more effective than placebo or amitriptyline in reducing migraine frequency, intensity, and duration over two to three months of treatment. No reliable information is available at longer-term follow-up. Our conclusion is that the use of SSRIs and SNRIs for migraine prophylaxis is not supported by evidence.

A systematic review of Chinese randomized clinical trials of SSRI treatment of depression.

BackgroundSelective serotonin reuptake inhibitors (SSRIs) have become the most frequently used antidepressants in China in recent decades. This systematic review and meta-analysis examined the efficacy and tolerability of SSRIs in Chinese studies and the quality of Chinese randomized controlled trials.MethodsMajor Western and Chinese electronic databases were searched for double-blind, parallel group randomised controlled trials (RCTs) comparing SSRIs (fluoxetine, citalopram, escitalopram, fluvoxamine, paroxetine, or sertraline) with other antidepressants such as SSRI, Selective Noradrenaline Reuptake Inhibitor (SNRI), tricyclic antidepressant (TCA), Traditional Chinese Medicine (TCM) and/or placebo. Response, remission, and dropout rates due to side effects were defined as primary outcomes. Mean total Hamilton Rating Scale of Depression (HAMD) scores at endpoint, overall dropout rates and total Treatment Emergent Symptom Scale (TESS) scores were defined as secondary outcomes. Data were combined with random effects models. Risk of bias was assessed by the Cochrane evaluation tool. Quality of reports was assessed by the fulfilment of Consolidated Standards of Reporting Trial (CONSORT) items.ResultsA total of 71 studies were included. Only one study was listed in both Chinese and Western databases. SSRIs were found to be more effective than TCAs. No significant differences were observed regarding dropout rates due to side effects. Using the Cochrane risk of bias tool, adequate methods of sequence generation were described in 16 (23%) studies. All authors failed to report trial registration. Informed consent, sources of funding, email address, protocol, and limitations were also not mentioned in most studies. However, reporting quality improved steadily between 1996 and 2013.ConclusionsIn light of the low trial quality, the findings of a significant advantage of SSRI over TCA in terms of response rate and remission rate should be replicated by large high-quality Chinese studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-014-0245-4) contains supplementary material, which is available to authorized users.

Selective Serotonin Reuptake Inhibitors in Autism

Awareness of the impact and prevalence of autism spectrum disorders has significantly increased in recent years. Given the dearth of reliable interventions, there is great interest in demonstrating efficacy of the various treatment options. A growing body of evidence links autism spectrum disorders to abnormalities in serotonin function, and the selective serotonin reuptake inhibitors (SSRIs) have been utilized to target various symptoms of the disorders. This article reviews the available data on the efficacy and tolerability of SSRIs in individuals with autism spectrum disorders. Objectives for future research in this area will also be suggested. The entire PubMed database including MEDLINE (1966-July 2005) was searched for English-language biomedical articles. Search terms included autism, autism spectrum disorder, citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, pervasive developmental disorder, selective serotonin reuptake inhibitors, and sertraline. All clinical trials evaluating treatment outcomes associated with the use of SSRIs in managing symptoms of autism that were identified in the search were reviewed. All randomized controlled trials and open-label trials were included in this review. Case reports and case series were excluded. We identified 3 randomized controlled trials and 10 open-label trials or retrospective chart reviews on the use of SSRIs in autism and autism spectrum disorders. The SSRIs that have been studied in autism spectrum disorders are citalopram, escitalopram, fluoxetine, fluvoxamine, and sertraline. Most studies demonstrate significant improvement in global functioning and in symptoms associated with anxiety and repetitive behaviors. While side effects were generally considered to be mild, increased activation and agitation occurred in some subjects. Although SSRIs may demonstrate therapeutic benefit in autism spectrum disorders, methodological weaknesses of many of the clinical trials suggest the need for additional randomized controlled trials. Furthermore, given the increased awareness of the dangers associated with SSRI-induced activation and agitation, the presence of these side effects in the autistic population warrants closer attention to dosage, titration, and subject selection issues.