Neuropsychiatric Disease and Treatment
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`Dovepress
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`Open access Full Text article
`
`Evaluation of the efficacy and safety of vilazodone
`for treating major depressive disorder
`
`O r i g i N a l
`r e s e a r c h
`
`Xiao-Fei Zhang
`lei Wu
`Dong-Jun Wan
`ruo-Zhuo liu
`Zhao Dong
`Min chen
`sheng-Yuan Yu
`Department of Neurology, chinese
`Pla general hospital, Beijing,
`People’s republic of china
`
`Purpose: Vilazodone is a novel serotonin (5-HT)-reuptake inhibitor and 5-HT1A partial
`agonist that was recently developed for the treatment of major depressive disorder (MDD).
`We conducted a meta-analysis and systematic review to better evaluate the efficacy and safety
`of vilazodone.
`Materials and methods: We performed a thorough literature search to identify all random-
`ized double-blind placebo-controlled trials that were designed to investigate the efficacy of
`vilazodone for the treatment of MDD, and that were published in electronic databases, including
`Medline, Embase, and the Cochrane Central Register of Controlled Trials. A manual search was
`also conducted to investigate the relevant references of the retrieved studies. Subsequently, we
`conducted a meta-analysis and systematic literature review.
`Results: A total of five randomized controlled trials were finally included, involving 1,200
`patients with vilazodone and 1,193 patients with placebo. The primary efficacy end point of the
`Montgomery–Åsberg Depression Rating Scale (standardized mean difference −3 .58, 95%
`confidence interval −4 .59 to −2 .56; P,0.00001), and the key secondary efficacy end points
`(Clinical Global Impression - Severity scale, Clinical Global Impression - Improvement scale,
`and Hamilton Anxiety Rating Scale) indicated that vilazodone was more effective than placebo.
`Most common adverse events, including diarrhea and nausea, were evaluated, and safety assess-
`ments indicated that vilazodone was well tolerated (diarrhea odds ratio 3.54, 95% confidence
`interval 2.81–4.45; P,0.00001; nausea odds ratio 3.85, 95% confidence interval 3.00–4.96;
`P,0.00001; discontinuations due to adverse events odds ratio 2.71, 95% confidence interval
`1.81–4.05; P,0.00001).
`Conclusion: Our findings indicate that the novel antidepressant vilazodone is effective and
`safe for MDD, with a low occurrence of side effects. It offers promise as an effective oral drug
`for the treatment of MDD, with a balance of efficacy and tolerability.
`Keywords: vilazodone, major depression, systematic review, antidepressant, randomized
`controlled trial
`
`Introduction
`Major depressive disorder (MDD) is a serious chronic and recurrent psychiatric
`illness, and accounts for 10%–14% of all patients seen by primary care physicians.1–3
`It is the third major cause of moderate-to-severe disability and worldwide burden of
`disease.4,5 The cardinal symptoms of MDD include diminished pleasure or interest in
`daily activities, changes
`in appetite or weight, sleep disorders, difficulty
`concentrating, fatigue, psychomotor agitation, sad mood, feelings of worthlessness,
`and even suicidal thoughts.6 Despite the current availability of different types of
`antidepressants, many patients with depression do not achieve adequate remission
`after treatment. Selective serotonin (5-HT)-reuptake inhibitors (SSRIs) are relatively
`effective treatments for MDD and the most commonly prescribed first-line treatment
`Merck 2005
` Argentum v. Merck
`options. Many patients
`IPR2018-00423
`
`1957
`Neuropsychiatric Disease and Treatment 2015:11 1957–1965
`© 2015 Zhang et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0)
`License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further
`permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information
`on how to request permission may be found at: http://www.dovepress.com/permissions.php
`
`correspondence: sheng-Yuan Yu
`Department of Neurology, chinese Pla
`general hospital, 28 Fuxing road, haidan
`District, Beijing 100853, People’s
`republic of china
`Tel/fax +86 10 68182255
`email yusy1963@126.com
`
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`Zhang et al
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`
`may show strong response to or tolerate a different SSRI7 if
`they do not adequately respond to or do not tolerate their ini-
`tial SSRI.8 Although all SSRIs modulate serotonin reuptake,
`they differ in their pharmacologic profiles, which may influ-
`ence efficacy and tolerability in individual patients. It is
`necessary to explore novel medications with superior clinical
`efficacy and good tolerability for patients with MDD.
`Vilazodone is a new antidepressant with a unique mecha-
`nism of action whereby it simultaneously acts as an SSRI
`and a 5-HT1A-receptor partial agonist.9–12 It was approved
`in 2011 by the US Food and Drug Administration for the
`treatment of MDD in adults.13 Clinicians have speculated that
`because vilazodone combines serotonin-reuptake inhibition
`and has a buspirone-like anxiolytic mechanism, it could be
`an effective and well-tolerated class of drug for patients with
`MDD symptoms.14,15
`The purpose of the present study was to review the
`currently available clinical studies referring to vilazodone
`and to summarize all the data to objectively evaluate the
`efficacy of this antidepressant for the treatment of MDD by
`meta-analysis.
`
`Materials and methods
`Data sources and search strategy
`All randomized controlled trials (RCTs) reporting the effect
`of vilazodone for treating MDD were systematically searched
`in the Medline, Embase, and Cochrane Central Register of
`Controlled Trials databases until April 2015. In our search
`strategy, the following keywords were used: “vilazodone”,
`
`“major depressive disorder”, and “randomized controlled
`trial”. In addition, a manual search was conducted to inves-
`tigate the relevant references of the retrieved publications.
`
`inclusion criteria
`All the selected articles were screened according to the fol-
`lowing criteria for inclusion: 1) articles referring to treatment
`with vilazodone for patients with MDD, 2) detailed data
`including the values of each index and the total number of
`each group available to be analyzed, 3) published as a full
`text up to April 2015. If the same author reported various
`articles sharing the identical case series, only the study with
`the most patients was used, and if the same research was
`published in different journals, only the most recent article
`was included for analysis. The flowchart depicting the study-
`selection process is presented in Figure 1.
`
`Quality assessment
`We assessed the methodological quality of each trial using
`the Jadad scale16 according to the following aspects: how
`the participants were allocated to the group of the studies,
`whether the articles stated explicitly the method of blind-
`ing, and whether they described the missing data due to
`attrition and explained the reason for dropouts. Based on
`the guidelines published in the Cochrane Handbook for
`Systematic Reviews of Interventions,17 each trial was then
`classified qualitatively and assigned to one of the three
`following rates: A, if the study met all quality criteria
`adequately and a low risk of bias was thought to exist; B,
`
`(cid:27)(cid:26)(cid:3)(cid:68)(cid:85)(cid:87)(cid:76)(cid:70)(cid:79)(cid:72)(cid:86)(cid:3)(cid:90)(cid:72)(cid:85)(cid:72)(cid:3)(cid:76)(cid:71)(cid:72)(cid:81)(cid:87)(cid:76)(cid:73)(cid:76)(cid:72)(cid:71)(cid:3)(cid:76)(cid:81)(cid:70)(cid:79)(cid:88)(cid:71)(cid:76)(cid:81)(cid:74)(cid:29)
`(cid:48)(cid:72)(cid:71)(cid:79)(cid:76)(cid:81)(cid:72)(cid:29)(cid:3)(cid:24)(cid:24)(cid:3)(cid:68)(cid:85)(cid:87)(cid:76)(cid:70)(cid:79)(cid:72)(cid:86)
`(cid:40)(cid:80)(cid:69)(cid:68)(cid:86)(cid:72)(cid:29)(cid:3)(cid:21)(cid:20)(cid:3)(cid:68)(cid:85)(cid:87)(cid:76)(cid:70)(cid:79)(cid:72)(cid:86)
`(cid:38)(cid:82)(cid:70)(cid:75)(cid:85)(cid:68)(cid:81)(cid:72)(cid:3)(cid:38)(cid:82)(cid:81)(cid:87)(cid:85)(cid:82)(cid:79)(cid:79)(cid:72)(cid:71)(cid:3)(cid:55)(cid:85)(cid:76)(cid:68)(cid:79)(cid:86)(cid:3)(cid:53)(cid:72)(cid:74)(cid:76)(cid:86)(cid:87)(cid:72)(cid:85)(cid:29)(cid:3)(cid:20)(cid:20)
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`
`(cid:50)(cid:81)(cid:3)(cid:87)(cid:75)(cid:72)(cid:3)(cid:69)(cid:68)(cid:86)(cid:76)(cid:86)(cid:3)(cid:82)(cid:73)(cid:3)(cid:87)(cid:76)(cid:87)(cid:79)(cid:72)(cid:86)(cid:3)(cid:68)(cid:81)(cid:71)
`(cid:68)(cid:69)(cid:86)(cid:87)(cid:85)(cid:68)(cid:70)(cid:87)(cid:86)(cid:15)(cid:3)(cid:26)(cid:24)(cid:3)(cid:68)(cid:85)(cid:87)(cid:76)(cid:70)(cid:79)(cid:72)(cid:86)(cid:3)(cid:90)(cid:72)(cid:85)(cid:72)
`(cid:72)(cid:91)(cid:70)(cid:79)(cid:88)(cid:71)(cid:72)(cid:71)
`
`(cid:54)(cid:72)(cid:89)(cid:72)(cid:81)(cid:3)(cid:68)(cid:85)(cid:87)(cid:76)(cid:70)(cid:79)(cid:72)(cid:86)(cid:3)(cid:90)(cid:72)(cid:85)(cid:72)(cid:3)(cid:81)(cid:82)(cid:87)(cid:3)(cid:53)(cid:38)(cid:55)(cid:86)
`
`(cid:41)(cid:76)(cid:89)(cid:72)(cid:3)(cid:68)(cid:85)(cid:87)(cid:76)(cid:70)(cid:79)(cid:72)(cid:86)(cid:3)(cid:90)(cid:76)(cid:87)(cid:75)(cid:3)(cid:73)(cid:76)(cid:89)(cid:72)(cid:3)(cid:53)(cid:38)(cid:55)(cid:86)(cid:3)(cid:90)(cid:72)(cid:85)(cid:72)(cid:3)(cid:76)(cid:81)(cid:70)(cid:79)(cid:88)(cid:71)(cid:72)(cid:71)(cid:3)(cid:76)(cid:81)(cid:3)(cid:87)(cid:75)(cid:72)(cid:3)(cid:73)(cid:76)(cid:81)(cid:68)(cid:79)(cid:3)(cid:68)(cid:81)(cid:68)(cid:79)(cid:92)(cid:86)(cid:76)(cid:86)
`(cid:70)(cid:82)(cid:80)(cid:83)(cid:68)(cid:85)(cid:76)(cid:81)(cid:74)(cid:3)(cid:89)(cid:76)(cid:79)(cid:68)(cid:93)(cid:82)(cid:71)(cid:82)(cid:81)(cid:72)(cid:3)(cid:90)(cid:76)(cid:87)(cid:75)(cid:3)(cid:83)(cid:79)(cid:68)(cid:70)(cid:72)(cid:69)(cid:82)(cid:3)(cid:76)(cid:81)(cid:3)(cid:48)(cid:39)(cid:39)
`
`Figure 1 Flow diagram of the study-selection process.
`Abbreviations: RCTs, randomized controlled trials; MDD, major depressive disorder.
`
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`
`Efficacy and safety of vilazodone for MDD
`
`40 mg/dayParticipants with haMa total score $20, haMa items 1 and 2
`
`10 weeks
`
`Oral
`
`223
`
`227
`
`Us
`
`Placebo
`
`Vilazodone
`
`severity scale.
`Abbreviations: MDD, major depressive disorder; MADRS, Montgomery–Åsberg Depression Rating Scale; HDRS-17, 17-item Hamilton Depression Rating Scale; HAMA, Hamilton Anxiety Rating Scale; CGI-S, Clinical Global Impression -
`et al24
`gommoll
`
`scores $2 and cgi-s score $4
`
`MaDrs total score $26
`episode lasting $8 weeks and up to 12 months, and had an
`
`40 mg/dayadults with MDD who had an ongoing major depressive
`
`8 weeks
`
`Oral
`
`281
`
`MaDrs total score $26
`episode lasting $8 weeks and up to 12 months, and had an
`
`40 mg/dayadults with MDD who had an ongoing major depressive
`
`8 weeks
`
`Oral
`
`252
`
`total score $22
`episode lasting $4 weeks and #2 years, and had an hDrs-17
`
`40 mg/dayadults with MDD who had an ongoing major depressive
`
`8 weeks
`
`Oral
`
`232
`
`284
`
`253
`
`231
`
`total score $22 and an hDrs-17 item single score $2
`episode lasting $4 weeks and #2 years, and had an hDrs-17
`
`40 mg/dayadults with MDD who had an ongoing major depressive
`
`8 weeks
`
`Oral
`
`Inclusion population
`
`Dosage
`
`treatment
`Duration of
`
`method
`Administration
`
`205
`ExperimentalControl
`
`205
`
`CountrySample size
`
`Us
`
`Us
`
`Us
`
`Us
`
`Placebo
`
`Vilazodone
`
`et al23
`Mathews
`
`Placebo
`
`croft et al22Vilazodone
`
`Placebo
`
`Khan et al21Vilazodone
`
`Placebo
`
`Vilazodone
`
`et al20
`rickels
`
`control group
`Therapy in
`
`Study
`Table 1 study and patient characteristics
`
`experimental group
`Therapy in
`
`submit your manuscript | www.dovepress.com
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`
`1959
`
`if the study partially met one or more of the quality criteria
`or the criteria were unclear and a moderate risk of bias
`was thought to exist; and C, if the study did not meet or
`include one or more of the criteria and a high risk of bias
`was thought to exist.
`
`Data extraction
`Usable information was collected from each paper: 1) first
`author’s name, 2) sample size, 3) country of the study, 4)
`year of publication, 5) therapy that the persons were treated
`with, and 6) data including the Montgomery–Åsberg Depres-
`sion Rating Scale (MADRS), Clinical Global Impression -
`Severity scale (CGI-S), CGI - Improvement scale (CGI-I),
`Hamilton Anxiety Rating Scale (HAMA), diarrhea, nausea,
`and discontinuations due to an adverse event (AE).
`
`statistical analysis
`Relevant data included in the meta-analysis were compared
`by using RevMan version 5.1.0.17 Differences between
`entry and completion of study were evaluated according
`to changes in MADRS, CGI-S, CGI-I, HAMA, diarrhea,
`nausea, and discontinuations due to an AE. We used the
`fixed-effect model (Mantel–Haenszel method) and random-
`effect model (DerSimonian–Laird method) to evaluate the
`standardized mean difference for continuous data and the
`relative risk for dichotomous results pooled across stud-
`ies with a corresponding 95% confidence interval (CI).18
`The study was considered to be homogeneous only when the
`analysis showed P.0.05, and then the fixed-effect model
`was chosen for meta-analysis; otherwise, the random-effect
`model was considered more appropriate. Inconsistency
`across studies was quantified by the I2 statistic, which
`describes the true extent of heterogeneity but not as a result
`of chance in results.19 I2 values ranged from 0% to 100%,
`representing a low level of heterogeneity if I2,25% and
`significant inconsistency if I2.50%.
`
`Results
`characteristics of included studies
`Initially, a total of 87 articles that may have offered usable
`data for our meta-analysis were included by the electronic
`and manual searches. We removed 75 studies after reviewing
`the titles and abstracts of the included articles according to
`the predefined inclusion and exclusion criteria. Among the
`remaining 12 articles, seven articles were excluded as not
`RCTs, and thus five RCTs20–24 that compared vilazodone with
`placebo were considered eligible for the analysis (Figure 1).
`The relevant information about the five included articles is
`listed in Table 1.
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`
`Abbreviation: iTT, intention-to-treat.
`used) – high risk of bias.
`Notes: Quality assessment rated as: A, all quality criteria met (adequate) – low risk of bias; B, one or more of the quality criteria only partly met (unclear) – moderate risk of bias; C, one or more criteria not met (inadequate or not
`gommoll et al24
`Mathews et al23
`croft et al22
`Khan et al21
`rickels et al20
`
`a
`
`a
`
`a
`
`a
`
`a
`
`of quality
`Level
`
`Yes
`Yes
`Yes
`Yes
`Yes
`analysis
`ITT
`
`analysis of covariance
`Mixed-effect model
`analysis of covariance
`analysis of covariance
`analysis of covariance
`analysis
`Statistical
`
`Yes
`Yes
`Yes
`Yes
`Yes
`sample size
`Calculation of
`
`19
`62
`120
`128
`101
`follow-up
`Loss to
`
`a
`
`a
`
`a
`
`a
`
`a
`
`a
`
`a
`
`a
`
`a
`
`a
`
`a
`
`a
`
`a
`
`a
`
`a
`
`Blinding
`
`concealment
`Allocation
`
`Study
`Table 2 Quality assessment of individual studies
`
`generation
`Allocation-sequence
`
`Quality of each study
`All of the studies included were double-blinded RCTs.
`Each described how to run the randomization processes and
`confirmed the optimal sample size by power-calculation
`methodologies (Table 2). The quality level of each study was
`A (Table 2). A funnel plot was performed through software
`to analyze whether the studies had statistical evidence of
`publication bias. It reflected the relationship between treat-
`ment effect and sample size for each included study. From
`the funnel plot, no significant publication bias was found
`(Figure 2).
`
`Efficacy
`To evaluate the efficacy of vilazodone for patients with
`MDD, we analyzed the data referring to MADRS, CGI-S,
`CGI-I, and HAMA. As for MADRS, only four of the five
`studies were included, representing 1,943 patients (973 in the
`vilazodone group and 970 for placebo), and the remaining
`indices were all studied in the five articles, which included
`2,393 patients (1,200 in the vilazodone group and 1,193 in
`the placebo group) (Figure 3). After the analysis, we got
`similar results for the indexes (MADRS, CGI-S, CGI-I, and
`HAMA): no significant heterogeneity was detected across
`studies (P.0.05 for all), and the fixed-effect model was
`then performed. As shown in Figure 3, the pooled estimates
`for standardized mean difference were −3.58, −0.33, −0.54,
`and −1.64 (95% CI −4.59 to −2.56, −0.41 to −0.25, −0.62
`to −0.46, and −2.07 to −1.22, respectively; P,0.00001
`for all). Based on the meta-analysis, it was proven that
`compared with placebo, vilazodone showed dramatically
`greater reductions in MADRS, CGI-S, CGI-I, and HAMA
`scores.
`
`safety
`As for the common AEs with vilazodone, diarrhea, nausea,
`and discontinuation due to AE data were evaluated in the
`five studies, including 2,393 participants (1,200 in the vila-
`zodone group and 1,193 in the placebo group) (Figure 4).
`In the subsequent analysis, effect size was expressed as
`odds ratios (ORs). Compared with the control group, five
`RCTs showed diarrhea data (OR 3.54, 95% CI 2.84–4.45;
`P,0.00001), nausea data (OR 3.85, 95% CI 3.00–4.96;
`P,0.00001), and discontinuation due to AE data (OR 2.71,
`95% CI 1.81–4.05; P,0.00001) (Figure 4). These results
`suggested that the incidences of diarrhea and nausea in the
`vilazodone group were higher than in the placebo group, and
`discontinuation due to AEs was significantly less likely to
`occur with the placebo.
`
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`Efficacy and safety of vilazodone for MDD
`
`Several articles reviewing the currently available studies
`about vilazodone showed that it was an effective and safe
`treatment option with its novel action mechanisms for
`patients with depression.35–37 We further evaluated similar
`aims through a meta-analysis, which was thought to be a
`reliable and objective approach. To our knowledge, this is the
`first study to conduct a thorough meta-analysis studying the
`efficacy and safety of vilazodone for treating MDD. Based
`on the meta-analysis, vilazodone at 40 mg per day proved
`to be superior to placebo in improving MADRS, CGI-S,
`CGI-I, and HAMA scores. Our study shows that treatment
`with vilazodone can offer both statistically significant and
`more importantly clinically satisfactory improvements
`for patients with MDD. Three of the RCTs evaluating the
`17-item Hamilton Depression Rating Scale (HDRS-17) also
`showed that vilazodone was superior to placebo in improving
`the symptoms of MDD.20,21,24 Among these, Rickels et al20
`analyzed the changes from baseline to end point in HDRS-17
`total score, which was significantly greater with vilazodone
`than with placebo (−10.4±0.6 versus −8.6±0.6, P=0.022).
`Khan et al21 reported the HDRS-17 response (defined
`as $50% decrease from baseline) was also significantly
`higher with treatment than placebo over 8 weeks (44.2%
`versus 32.9%, P=0.013). Recently, similar results on the same
`index were reported, although they did not reach statistical
`significance (−5.56 versus −4.67, P=0.0863).24 In addition,
`Robinson et al38 demonstrated that 40 mg per day for 1 year
`was also safe and well tolerated by adults with MDD.
`The unique dual mechanism of action for vilazodone
`can shorten the onset of antidepressant activity along with
`enhanced remission and response rates, which may explain
`the satisfactory clinical efficacy and decreased side effects
`attributed to serotonin-reuptake inhibition, and provide
`enhanced benefits for symptoms of anxiety.14,15,21
`Side effects, such as diarrhea, nausea, and discontinua-
`tions due to AEs, induced by vilazodone were higher than pla-
`cebo. Gastrointestinal AE incidence in the current study was
`consistent with observations from vilazodone-registration
`studies. Similarly to prior studies, most instances of
`vilazodone-related diarrhea and nausea were mild or mod-
`erate in intensity, led to few premature discontinuations,
`occurred within the first few weeks of treatment, and were
`transient in nature. Overall, treatment with vilazodone was
`well tolerated. Furthermore, the incidence of markedly
`abnormal laboratory or vital sign changes was low and similar
`between the treatment groups.
`The meta-analysis included only studies with all data
`derived from randomized, double-blind, placebo-controlled
`
`(cid:177)(cid:20)(cid:19)
`(cid:19)
`(cid:20)(cid:19)
`(cid:55)(cid:85)(cid:72)(cid:68)(cid:87)(cid:80)(cid:72)(cid:81)(cid:87)(cid:3)(cid:72)(cid:73)(cid:73)(cid:72)(cid:70)(cid:87)(cid:3)(cid:82)(cid:73)(cid:3)(cid:43)(cid:36)(cid:48)(cid:36)(cid:3)(cid:73)(cid:82)(cid:85)(cid:3)(cid:72)(cid:68)(cid:70)(cid:75)(cid:3)
`(cid:76)(cid:81)(cid:70)(cid:79)(cid:88)(cid:71)(cid:72)(cid:71)(cid:3)(cid:86)(cid:87)(cid:88)(cid:71)(cid:92)(cid:3)(cid:11)(cid:48)(cid:39)(cid:12)
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`(cid:21)(cid:19)
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`(cid:21)(cid:19)
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`(cid:54)(cid:68)(cid:80)(cid:83)(cid:79)(cid:72)(cid:3)(cid:86)(cid:76)(cid:93)(cid:72)(cid:3)(cid:73)(cid:82)(cid:85)(cid:3)(cid:72)(cid:68)(cid:70)(cid:75)(cid:3)(cid:76)(cid:81)(cid:70)(cid:79)(cid:88)(cid:71)(cid:72)(cid:71)(cid:3)
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`(cid:86)(cid:87)(cid:88)(cid:71)(cid:92)(cid:3)(cid:11)(cid:54)(cid:40)(cid:3)(cid:62)(cid:48)(cid:39)(cid:64)(cid:12)
`
`Figure 2 Funnel-plot analysis to detect publication bias.
`Notes: each circle represents the indicated association between treatment effect
`and sample size for an individual study.
`Abbreviations: MD, mean difference; SE, standard error.
`
`Discussion
`Depression is the most common psychiatric disorder and a
`leading cause of disability worldwide.25,26 It is reported that
`an estimated 8 million individuals meet criteria for MDD,
`and about 10% of the adult population experiences a major
`depressive episode each year in the US.27,28 Changes in
`cognitive–emotional and physical symptoms of depression
`translate to extensive impairments in psychosocial function-
`ing across physical, occupational, and social domains that
`severely affect the patient’s quality of life.29,30 The likelihood
`of long-term treatment success is improved with early, quick,
`and accurate diagnosis, multidimensional assessment, and
`rational pharmacotherapy tailored to each patient’s symp-
`tomatology, coexisting disorders, and treatment needs.31 The
`first-generation antidepressants are classified as monoamine
`oxidase inhibitors (MAOIs) and tricyclic antidepressants
`(TCAs).32 The side-effect profile of these two drug classes
`is one of the major factors that limit their use. Compared
`with MAOIs and TCAs, in general SSRIs have been found
`to show similar efficacy in the treatment of depressed outpa-
`tients, with a better tolerability profile.33 As a result, TCAs
`and MAOIs were rapidly supplanted by SSRIs as the first
`choice for both psychiatrists and primary care providers for
`treating depression.34
`Vilazodone, which is the first of a new class of antidepres-
`sants called indolealkylamines, has been approved for the
`treatment of MDD and has dual-acting properties combining
`SSRI and 5-HT1A partial agonist activity.13 On the basis of
`its unique action mechanism for patients with depression,
`vilazodone offers the potential advantage of faster treatment
`effect with lower AE risks characterized by good tolerability
`compared with currently used antidepressants.
`
`Neuropsychiatric Disease and Treatment 2015:11
`
`submit your manuscript | www.dovepress.com
`Dovepress
`
`1961
`
`

`

`Zhang et al
`
`Dovepress
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`(cid:177)(cid:19)(cid:17)(cid:23)(cid:19)(cid:3)(cid:11)(cid:177)(cid:19)(cid:17)(cid:25)(cid:27)(cid:3)(cid:87)(cid:82)(cid:3)(cid:177)(cid:19)(cid:17)(cid:20)(cid:21)(cid:12)(cid:21)(cid:19)(cid:19)(cid:28)
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`(cid:20)(cid:19)(cid:19)(cid:8)
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`(cid:177)(cid:21)(cid:17)(cid:27)(cid:19)(cid:3)(cid:11)(cid:177)(cid:23)(cid:17)(cid:25)(cid:20)(cid:3)(cid:87)(cid:82)(cid:3)(cid:177)(cid:19)(cid:17)(cid:28)(cid:28)(cid:12)(cid:21)(cid:19)(cid:20)(cid:24)
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`(cid:177)(cid:22)(cid:17)(cid:22)(cid:19)(cid:3)(cid:11)(cid:177)(cid:24)(cid:17)(cid:24)(cid:21)(cid:3)(cid:87)(cid:82)(cid:3)(cid:177)(cid:20)(cid:17)(cid:19)(cid:27)(cid:12)(cid:21)(cid:19)(cid:19)(cid:28)
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`
`CI, confidence interval.
`Abbreviations: MADRS, Montgomery–Åsberg Depression Rating Scale; CGI-S, Clinical Global Impression - Severity scale; CGI-I, CGI - Improvement scale; HAMA, Hamilton Anxiety Rating Scale; SD, standard deviation; IV, inverse variance;
`Figure 3 Forest plots showing changes in (A) the MaDrs, (B) the cgi-s, (C) the cgi-i, and (D) haMa in the treatment studies.
`
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