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Mean Change From Baseline in Number of Panic Attacks per Week at Each Week and Endpoint (Observed Cases) for Patients With Panic Disorder Who Received Sertraline or Placebo a
Source publication
This study determined the efficacy and safety of sertraline in the treatment of patients with panic disorder.
The study was a randomized, double-blind, parallel-group, flexible-dose comparison of sertraline and placebo in outpatients with a DSM-III-R diagnosis of panic disorder with or without agoraphobia. After a 2-week single-blind placebo lead-i...
Contexts in source publication
Context 1
... study's primary efficacy measure was the number of panic attacks per week, de- rived from the Panic and Anticipatory Anxiety Scale. The mean change from baseline in the number of panic attacks per week is presented in figure 1. At endpoint, the average percentage decrease from baseline in num- ber of panic attacks was 77% for the sertraline-treated patients and 51% for the placebo-treated patients. ...
Context 2
... the number of limited-symptom attacks per week is presented in fig- ure 2. The mean number of limited-symptom attacks per week decreased by 5.9 (SD=8.8) in the sertraline group and 2.4 (SD=7.0) in the placebo group; the re- duction in limited-symptom attacks at endpoint was significantly greater in the sertraline group than in the placebo group (F=6.08, df=1, 145, ...
Context 3
... endpoint the sertraline-treated patients showed more improvement than the placebo-treated patients on the Hamilton Anxiety Rating Scale, but the reduc- tions of the two groups were not statistically different (F=4.71, df=1, 145, ...
Context 4
... improvement at endpoint in the pa- tients treated with sertraline than in the placebo- treated patients (severity: F=13.35, df=1, 145, p< 0.001; improvement: F=15.83, df=1, 146, p<0.001). On the CGI improvement subscale for panic attacks, the sertraline-treated patients showed significantly more improvement than did the patients taking pla- cebo (F=14.27, df=1, 146, p<0.001). The sertraline- treated patients also showed more improvement than the placebo-treated patients on the other four CGI sub- scales, but the differences between treatment groups did not reach statistical significance (anticipatory anxiety: F=4.81, df=1, 146, p=0.03; phobic avoidance: F=4.50, df=1, 146, p=0.04; social/family ...
Citations
... Intention-to-treat data were prioritized (80 studies 30-35,37-58,60-65,67-74,76-78,80,81, 83-96, 98, 99, 101, 102, 104-112, 114, 115 ); if not available, data from observed patients were used. 36,59,66,75,79,82,97,100,103,113 Dropout rates will be presented in a separate publication. ...
... An overview of the 90 RCTs 30-115 included in the metaanalysis is provided in Table 2. A total of 9985 placebotreated study participants were included, distributed across the 9 diagnoses as follows: 1598 participants with MDD, 30-39 967 participants with mania, 40-46 888 participants with schizophrenia, 47-56 803 participants with OCD, 57-66 1189 participants with ADHD, 67-76 1457 participants with GAD, 77-85 1180 participants with social phobia, [86][87][88][89][90][91][92][93][94][95] 1248 participants with panic disorder, [96][97][98][99][100][101][102][103][104][105] and 655 participants with PTSD. [106][107][108][109][110][111][112][113][114][115] There was no indication of small-study effects or publication bias based on findings from a funnel plot (eFigure in Supplement 1) or from Egger test (P = .95). ...
Importance
Placebo is the only substance systematically evaluated across common psychiatric diagnoses, but comprehensive cross-diagnostic comparisons are lacking.
Objective
To compare changes in placebo groups in recent high-quality randomized clinical trials (RCTs) across a broad spectrum of psychiatric disorders in adult patients.
Data Sources
MEDLINE and the Cochrane Database of Systematic Reviews were systematically searched in March 2022 for the latest systematic reviews meeting predetermined high-quality criteria for 9 major psychiatric diagnoses.
Study Selection
Using these reviews, the top 10 highest-quality (ie, lowest risk of bias, according to the Cochrane Risk of Bias tool) and most recent placebo-controlled RCTs per diagnosis (totaling 90 RCTs) were selected, adhering to predetermined inclusion and exclusion criteria.
Data Extraction and Synthesis
Following the Cochrane Handbook, 2 authors independently carried out the study search, selection, and data extraction. Cross-diagnosis comparisons were based on standardized pre-post effect sizes (mean change divided by its SD) for each placebo group. This study is reported following the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline.
Main Outcome and Measure
The primary outcome, pooled pre-post placebo effect sizes ( d av ) with 95% CIs per diagnosis, was determined using random-effects meta-analyses. A Q test assessed statistical significance of differences across diagnoses. Heterogeneity and small-study effects were evaluated as appropriate.
Results
A total of 90 RCTs with 9985 placebo-treated participants were included. Symptom severity improved with placebo in all diagnoses. Pooled pre-post placebo effect sizes differed across diagnoses ( Q = 88.5; df = 8; P < .001), with major depressive disorder ( d av = 1.40; 95% CI, 1.24-1.56) and generalized anxiety disorder ( d av = 1.23; 95% CI, 1.06-1.41) exhibiting the largest d av . Panic disorder, attention-deficit/hyperactivity disorder, posttraumatic stress disorder, social phobia, and mania showed d av between 0.68 and 0.92, followed by OCD ( d av = 0.65; 95% CI, 0.51-0.78) and schizophrenia ( d av = 0.59; 95% CI, 0.41-0.76).
Conclusion and Relevance
This systematic review and meta-analysis found that symptom improvement with placebo treatment was substantial in all conditions but varied across the 9 included diagnoses. These findings may help in assessing the necessity and ethical justification of placebo controls, in evaluating treatment effects in uncontrolled studies, and in guiding patients in treatment decisions. These findings likely encompass the true placebo effect, natural disease course, and nonspecific effects.
... Sertralin war ebenfalls in DBPK-Studien (Londborg et al., 1998;Pohl et al., 1998;Pollack et al., 1998) und in einer noninferiority-Vergleichsstudie (Bandelow et al., 2004a) wirksam. Eine Studie fand keinen Unterschied zu Placebo (Koszycki et al., 2011). ...
... Judge, 1997 ;Pollack et al., 2007a ;Wedekind et al., 2010) = clomipramine (Bakker et al., 1999 ;Lecrubier u. Judge, 1997) = sertraline (Bandelow et al., 2004a) < venlafaxine (Pollack et al., 2007a) = venlafaxine (Pollack et al., 2007b) Sertraline > placebo (Londborg et al., 1998;Pohl et al., 1998;Pollack et al., 1998;Rapaport et al., 2001) = paroxetine (Bandelow et al., 2004a) = placebo (Kamijima et al., 2005;Koszycki et al., 2011) Referenzleitlinien The relative efficacy and tolerability of differing pharmacological treatments is uncertain, but there may be (…) tolerability disadvantages for fluvoxamine (I (M)) All SSRIs are recommended as an evidence-based acute treatment (A) ...
... − Imipramin war wirksam in placebokontrollierten Studien (Klein, 1964;Zitrin et al., 1980;Zitrin et al., 1983) und Referenzvergleichen (CNCPS, 1992;Gentil et al., 1993;Nair et al., 1996;Sheehan et al., 1990;Uhlenhuth et al., 1989). In einer Studie ohne ausreichende Teststärke waren Imipramin und Buspiron auf dem Hauteffizienzmaß nicht wirksamer als Placebo (Pohl et al., 1998). In einer Rückfallpräventionsstudie (8 Wochen Akutphase, gefolgt von einer bis zu 35 Wochen dauernden Rückfallprävention) war Imipramin gegenüber Placebo überlegen und ebenso wirksam wie Alprazolam (Curtis et al., 1993). ...
... The PQ-LES-Q was adapted from the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), a 93-item self-report measure intended for adults [17]. The adult version has consistently demonstrated high reliability and validity [17][18][19]. It has adequate internal validity and sensitive to change [20,21]. ...
... ARQ 49 was used due to acceptable psychometrics for the current sample [27]. The original ARQ is an 88-item self-report measure for adolescents (11)(12)(13)(14)(15)(16)(17)(18)(19) years old) to assess both individual and environmental factors that contribute to resilience [7]. The measure assesses resilience from the individual domain and from several environmental domains (family, peers, school, and community). ...
Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire is a brief 15-item self-report measure of quality of life and life satisfaction originally developed for clinical populations (6 to 17 years old). The current paper examines the initial factor structure proposed by the developers and underlying psychometric properties of the measure in a non-clinical population of teens. A cross-sectional adolescent sample (N = 3222) completed self-report measures as part of mental health promotion program. A confirmatory factor analysis was conducted with construct validity analyses. The original factor structure was replicated with strong internal consistency (Cronbach α = .912). Strong construct validity (e.g. resilience, well-being, depression, and anxiety) was found. Minimal differences were found based on gender, race, and ethnicity. PQ-LES-Q has strong, replicable psychometric properties, which makes it a generally reliable and valid assessment tool to evaluate the quality of life and life satisfaction in adolescents.
... Serotonergic antidepressants are also associated with significant sexual side-effects that can limit tolerability and impact adherence (16)(17)(18)(19). Although typically quite well-tolerated, serotonergic antidepressants are associated with other common adverse effects include nausea, diarrhea, diaphoresis, headaches, tremor, asthenia, insomnia, and somnolence (20)(21)(22)(23)(24)(25). Finally, sudden discontinuation of these serotonergic antidepressants can result in a withdrawal syndrome which can include worsening of anxiety symptoms, panic attacks, dizziness, nausea that can be quite substantial and may take several few weeks to resolve without treatment (26). ...
Serotonin reuptake inhibitors and benzodiazepines are evidence-based pharmacological treatments for Anxiety Disorders targeting serotonin and GABAergic systems, respectively. Although clearly effective, these medications fail to improve anxiety symptoms in a significant proportion of patients. New insights into the glutamate system have directed attention toward drugs that modulate glutamate as potential alternative treatments for anxiety disorders. Here we summarize the current understanding of the potential role of glutamate neurotransmission in anxiety disorders and highlight specific glutamate receptors that are potential targets for novel anxiety disorder treatments. We also review clinical trials of medications targeting the glutamate system in DSM-5 anxiety disorders. Understanding the role of the glutamate system in the pathophysiology of anxiety disorder may aid in developing novel pharmacological agents that are effective in treating anxiety disorders.
... In clinical practice, SSRIs and serotonin has been used widely to treat PD [21]. For example, the sertraline is significantly superior to placebo for PD patients, and the incidence of adverse events was not different between sertraline and placebo [22][23][24]. Hence, in this study, The main aim of this study was to investigate the association of candidate genes from both serotonergic pathways including regulatory and coding variants of the SLC6A4, 5-HTR1A, 5-HTR2A and COMT genes. ...
Objective The aim of the present study was to examine the association of serotonin -related gene polymorphisms with PD risk. Then, we analyzed the correlation between these gene polymorphisms and response to sertraline drug.
Methods 230 patients with PD and 231 healthy controls were enrolled in the study. Panic Disorder Severity Scale (PDSS) were administered to all subjects, and all patients in the study were also assessed after 4 weeks of treatment. The SLC6A4(rs140701, rs3813034, 5-HTTLPR and STin2), HTRA1 rs6295, HTR2A rs6313 and COMT rs4680 genes were genotyped and assessed for allele.
Results The allelic model showed that the SLC6A4 rs140701 variant was significantly associated with increased risk of PD(OR = 0.624, 95% CI 0.450-0.864, p <0.05), and significant results was found in the dominant model(OR = 0.546; 95% CI, 0.371-0.804, p <0.05). There was a significant difference in allele and genotype frequency between responders and nonresponders in the 5-HTTLPR polymorphism (OR = 0.205, 95% CI 0.128-0.328; OR = 0.249, 95% CI 0.155-0.401, both p <0.001), and indicated the PD patients with S-allele had a poorer response to sertraline than L-allele carriers.
Conclusions The present study suggest that the SLC6A4 rs140701 variant may be associated with susceptibility to PD, and 5-HTTLPR polymorphism may be a predictor of response to sertralines in the treatment of PD.
... Out of 382 citations identified by the database search, 242 were eligible for inclusion and 148 of these trials provided sufficient data for the meta-analysis. Table 1 depicts the characteristics of the included trials (Alaka et al., 2014;Allgulander, 1999;Allgulander et al., 2004a;Allgulander et al., 2004b;Alvarez et al., 2012;Asakura et al., 2007;Asnis et al., 2001;Nicolini et al., 2009;Nierenberg et al., 2007;Nimatoudis et al., 2004;Oehrberg et al., 1995;Perahia et al., 2006;Pohl et al., 1998;Pollack et al., 2007a;Pollack et al., 2007b;Pollack et al., 1998;Pollack et al., 2001;Reimherr et al., 1998;Rickels et al., 1989;Rickels et al., 2009;Rickels et al., 2004;Rickels et al., 2000;Rickels et al., 2003;Rudolph and Feiger, 1999;Rynn et al., 2008;Schutters et al., 2010;Sheehan et al., 2005;Silverstone and Ravindran, 1999;Silverstone and Salinas, 2001;Stahl, 2000;Stahl et al., 2003;Stein et al., 2007aStein et al., , 2007bStein et al., 1999;Stein et al., 1998;Stein et al., 2005;Steiner et al., 2005;Thase, 1997;Tollefson et al., 1994;Tourian et al., 2009;Trivedi et al., 2004;Trivedi et al., 2001;Van Ameringen et al., 2001;van Vliet et al., 1994;Vartiainen and Leinonen, 1994;Wade et al., 1997;Wade et al., 2002;Westenberg et al., 2004;Zohar and Judge, 1996;Zung et al., 1983). ...
... Ten studies investigated the adverse event of nausea in acute PD patients, comparing 1353 acute PD patients treated with SSRIs and 797 acute PD patients treated with placebo (Asnis et al., 2001;Ballenger et al., 1998;Lecrubier et al., 1997;Londborg et al., 1998;Michelson et al., 2000;Pohl et al., 1998;Pollack et al., 1998;Sandmann et al., 1995;Sheik et al., 2000;Wade et al., 1997). SSRIs increased the risk of nausea (OR=1.68; ...
... The SSRI investigation on diarrhea were conducted in 1405 PD patients (Ballenger et al., 1998;Lecrubier et al., 1997;Londborg et al., 1998;Pohl et al., 1998;Pollack et al., 1998;Sandmann et al., 1995;Sheikh et al., 2000). A total of 889 acute PD patients were treated with SSRIs, and 516 were taking placebo. ...
... Seven studies assessed SSRIs and placebo regarding sexual dysfunction (Ballenger et al., 1998;Lecrubier et al., 1997; , 1998;Pohl et al., 1998;Pollack et al., 1998;Sheik et al., 2000;Wade et al., 1997). Of these, one evaluated anorgasmia (Wade et al., 1997) in 281 SSRI and 96 placebo-treated patients with acute PD, while the others investigated abnormal ejaculation in 866 SSRI and 493 short-term placebo-treated patients (Ballenger et al., 1998;Lecrubier et al., 1997;Londborg et al., 1998;Pohl et al., 1998;Pollack et al., 1998;Sheikh et al., 2000b). ...
Background: Benzodiazepines (BZs) and selective serotonin reuptake inhibitors (SSRIs) are effective in the pharmacologic treatment of panic disorder
(PD). However, treatment guidelines favor SSRIs over BZs based on the belief that BZs are associated with more adverse effects than SSRIs. This belief,
however, is currently supported only by opinion and anecdotes.
Aim: The aim of this review and meta-analysis was to determine if there truly is evidence that BZs cause more adverse effects than SSRIs in acute PD
treatment.
Methods: We systematically searched Web of Science, PubMed, Cochrane Central Register of Controlled Trials, and clinical trials register databases.
Short randomized clinical trials of a minimum of four weeks and a maximum of 12 weeks that studied SSRIs or BZs compared to placebo in acute PD
treatment were included in a meta-analysis. The primary outcome was all-cause adverse event rate in participants who received SSRIs, BZs, or placebo.
Results: Overall, the meta-analysis showed that SSRIs cause more adverse events than BZs in short-term PD treatment. Specifically, SSRI treatment
was a risk factor for diaphoresis, fatigue, nausea, diarrhea, and insomnia, whereas BZ treatment was a risk factor for memory problems, constipation,
and dry mouth. Both classes of drugs were associated with somnolence. SSRIs were associated with abnormal ejaculation, while BZs were associated
with libido reduction. BZs were protective against tachycardia, diaphoresis, fatigue, and insomnia.
Conclusion: Randomized, blinded studies comparing SSRIs and BZs for the short-term treatment of PD should be performed. Clinical guidelines based
on incontrovertible evidence are needed.
... Pohl [16] and Pollack [17] A double-blind, long-term study by Kamijima et al. [18] evaluated the efficacy and safety of sertraline for 8 weeks in Japanese patients with PD. Three hundred and ninety-four patients were initially treated with 8 weeks of open-label sertraline followed by 8 weeks of double-blind treatment with either placebo or sertraline (50-100mg/day). ...
... The plethora of welldocumented biological substrates, receptors, and pathways for serotonin are candidates to mediate the therapeutic actions and side effects of SSRIs. Across published studies, adverse events reported more frequently by patients receiving SSRIs than those receiving placebo were sudoresis, diarrhea, nausea, vomiting, and sexual dysfunction [10,14,16]. Dry mouth, dyspepsia, headache [10,14,15], tremor, asthenia, drowsiness, and insomnia [14,20] were also reported as side effects of SSRIs in PD. ...
Introduction: Panic disorder (PD) is a prevalent and disabling anxiety disorder that can be treated effectively. Selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines are among the most frequently prescribed drugs for PD. In this article, the authors review the current evidence on efficacy, adverse events, and limitations of these two treatment options.
Areas covered: MEDLINE/Pubmed and Web of Science databases were searched for open or placebo-controlled trials on SSRIs and/or benzodiazepines in PD treatment.
Expert opinion: The literature search yielded 4,957 articles related to the theme. Of these, 24 articles were included in this review. Despite their usefulness in PD, SSRIs are associated with a delay of several weeks in onset of therapeutic effect and have the potential to exacerbate anxiety and panic early in the treatment course. Benzodiazepines present rapid onset of action, but can cause tolerance and dependence. Despite strong evidence of the effectiveness of SSRIs and benzodiazepines in the treatment of PD, few trials have performed head-to-head comparisons of these two drug classes. Future studies on the pharmacological treatment of PD should make direct comparisons of risks, benefits, and limitations of each group. This could help improve the evidence-based pharmacotherapy of PD.
... Although jitteriness/anxiety syndrome is known to be potentially caused by the use of antidepressants in general, it occurs rarely in patients specifically treated with sertraline. In a prior study, Pohl et al. reported no significant differences in the occurrence between patients administered sertraline and those administered placebo [2]. However, we encountered two cases in which both the patients developed jitteriness/anxiety syndrome on the day after initiation of a regimen of sertraline. ...
... Jitteriness/anxiety syndrome occurs with antidepressants in general [3], and there have also been reports of sertraline causing jitteriness/anxiety syndrome [4], though this is generally considered very rare [2]. However, we experienced two cases of jitteriness/anxiety syndrome developing immediately following the initiation of administration at low doses of sertraline. ...
... Although considered rare [2], the prevalence of sertraline-induced jitteriness/anxiety syndrome remains to be investigated. It might be overlooked in some cases, because such symptoms could be mistaken as psychiatric symptoms if psychiatrists are not aware of its occurrence. ...
Here, we report our experience with patients in whom jitteriness/anxiety syndrome developed immediately following the start of oral sertraline administration. Administration was discontinued in these patients on day 2, and the jitteriness/anxiety syndrome improved the following day. Jitteriness/anxiety syndrome may develop immediately following oral administration of even low doses of sertraline, and improvement can be expected if sertraline is promptly discontinued.
... Recommended dosages are 20 mg/day. Concerning sertraline, studies have shown that gradually reaching a maximal dose of 125 mg/day may maximize the efficacy and minimize the side effects such as ejaculation, orgasmic disorders, dry mouth, agitation or nervousness [60,61]. Citalopram has shown good efficacy at doses of 20 to 60 mg/day, however the best benefit risk ratio is obtained after three months [62][63][64]. ...
Anxiety disorders are the most prevalent psychiatric disorders. There is a high comorbidity between anxiety (especially generalized anxiety disorders or panic disorders) and depressive disorders or between anxiety disorders, which renders treatment more complex. Current guidelines do not recommend benzodiazepines as first-line treatments due to their potential side effects. Selective serotonin reuptake inhibitors and selective serotonin norepinephrine reuptake inhibitors are recommended as first-line treatments. Psychotherapy, in association with pharmacotherapy, is associated with better efficacy. Finally, a bio-psycho-social model is hypothesized in anxiety disorders.
